Regulatory myeloid cells: an underexplored continent in B-cell lymphomas
AbstractIn lymphomas arising from the germinal center, prognostic factors are linked to the myeloid compartment. In particular, high circulating monocyte or myeloid-derived suppressor cell counts are associated with poor prognosis for patients with high-grade B-cell lymphomas. Macrophages with an M2 phenotype are enriched within lymphoma tumors. However, the M1/M2 nomenclature is now deprecated and the clinical impact of this phenotype remains controversial. Across cancer types, myeloid cells are primarily thought to function as immune suppressors during tumor initiation and maintenance, but the biological mechanisms behin...
Source: Cancer Immunology, Immunotherapy - July 8, 2017 Category: Cancer & Oncology Source Type: research

Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer
This study sought to evaluate whether myeloid-derived suppressor cells (MDSC) could be affected by chemotherapy and correlate with pathologic complete response (pCR) in breast cancer patients receiving neo-adjuvant chemotherapy. Peripheral blood levels of granulocytic (G-MDSC) and monocytic (M-MDSC) MDSC were measured by flow cytometry prior to cycle 1 and 2 of doxorubicin and cyclophosphamide and 1st and last administration of paclitaxel or paclitaxel/anti-HER2 therapy. Of 24 patients, 11, 6 and 7 patients were triple negative, HER2+ and hormone receptor+, respectively. 45.8% had pCR. Mean M-MDSC% were
Source: Cancer Immunology, Immunotherapy - July 7, 2017 Category: Cancer & Oncology Source Type: research

Immune biomarkers for chronic inflammation related complications in non-cancerous and cancerous diseases
AbstractChronic inflammation arising in a diverse range of non-cancerous and cancerous diseases, dysregulates immunity and exposes patients to a variety of complications. These include immunosuppression, tissue damage, cardiovascular diseases and more. In cancer, chronic inflammation and related immunosuppression can directly support tumor growth and dramatically reduce the efficacies of traditional treatments, as well as novel immune-based therapies, which require a functional immune system. Nowadays, none of the immune biomarkers, regularly used by clinicians can sense a developing chronic inflammation, thus complication...
Source: Cancer Immunology, Immunotherapy - July 3, 2017 Category: Cancer & Oncology Source Type: research

The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity
AbstractThe primary aim of this clinical trial was to determine the feasibility of delivering first-generation CAR T cell therapy to patients with advanced, CEACAM5+ malignancy. Secondary aims were to assess clinical efficacy, immune effector function and optimal dose of CAR T cells. Three cohorts of patients received increasing doses of CEACAM5+-specific CAR T cells after fludarabine pre-conditioning plus systemic IL2 support post T cell infusion. Patients in cohort 4 received increased intensity pre-conditioning (cyclophosphamide and fludarabine), systemic IL2 support and CAR T cells. No objective clinical responses were...
Source: Cancer Immunology, Immunotherapy - June 28, 2017 Category: Cancer & Oncology Source Type: research

LILRB receptor-mediated regulation of myeloid cell maturation and function
AbstractThe leukocyte immunoglobulin-like receptor (LILR) family comprises a set of paired immunomodulatory receptors expressed among human myeloid and lymphocyte cell populations. While six members of LILR subfamily A (LILRA) associate with membrane adaptors to signal via immunoreceptor tyrosine-based activating motifs  (ITAM), LILR subfamily B (LILRB) members signal via multiple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIM). Ligand specificity of some LILR family members has been studied in detail, but new perspective into the immunoregulatory aspects of this receptor family in human myeloid cel...
Source: Cancer Immunology, Immunotherapy - June 21, 2017 Category: Cancer & Oncology Source Type: research

Critical biological parameters modulate affinity as a determinant of function in T-cell receptor gene-modified T-cells
AbstractT-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity. It is critical to re-evaluate the importance of other bi...
Source: Cancer Immunology, Immunotherapy - June 20, 2017 Category: Cancer & Oncology Source Type: research

Autoimmune diabetes induced by PD-1 inhibitor —retrospective analysis and pathogenesis: a case report and literature review
We report a case of autoimmune diabetes related to nivolumab treatment. A 73-year-old man was treated in second line with ni volumab at 3 mg/kg every two weeks for metastatic melanoma. At 6 weeks of treatment, he displayed diabetic ketoacidosis. Nivolumab was withheld 3.5 weeks and insulin therapy was initiated, enabling a normalization of glycaemia and the disappearance of symptoms. Laboratory investigations demonstra ted the presence of islet cell autoantibodies, while C-peptide was undetectable. Retrospective explorations on serum banked at week 0 and 3 months before the start of nivolumab, already s...
Source: Cancer Immunology, Immunotherapy - June 20, 2017 Category: Cancer & Oncology Source Type: research

Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions
AbstractTrastuzumab is the first-line drug to treat breast cancer with high Her2 expression. However, many cancers failed to respond, largely due to their resistance to NK cell-triggered antibody-dependent cellular cytotoxicity (ADCC). Poliovirus receptor (PVR)-like molecules are known to be important for lymphocyte functions. We found that all PVR-like receptors are expressed on human NK cells, and only TIGIT is preferentially expressed on the CD16+ NK cell subset. Disrupting the interactions of PVR-like receptors with their ligands on cancer cells regulates NK cell activity. More importantly, TIGIT is upregulated upon NK...
Source: Cancer Immunology, Immunotherapy - June 16, 2017 Category: Cancer & Oncology Source Type: research

A phase II study of ipilimumab plus temozolomide in patients with metastatic melanoma
AbstractCheckpoint blockade has revolutionized the treatment of melanoma; however, it benefits only the minority of patients. Several agents have been combined with immunotherapy to improve T-cell activation and persistence including growth factor, chemotherapy, and radiation. Preclinical data suggest that temozolomide, which metabolizes to the same active compound as dacarbazine, selectively depletes regulatory T cells. This potential immunomodulatory effect of temozolomide provides rationale for combination with ipilimumab. We performed an open-label single-arm phase II study of ipilimumab plus temozolomide in the frontl...
Source: Cancer Immunology, Immunotherapy - June 13, 2017 Category: Cancer & Oncology Source Type: research

Phase I trial of antigen-targeted autologous dendritic cell-based vaccine with in vivo activation of inducible CD40 for advanced prostate cancer
AbstractThis phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bi...
Source: Cancer Immunology, Immunotherapy - June 12, 2017 Category: Cancer & Oncology Source Type: research

TGF- β1-silenced leukemia cell-derived exosomes target dendritic cells to induce potent anti-leukemic immunity in a mouse model
AbstractTumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from theTGF-β1 silenced L1210 cells (LEXTGF- β1si) can enhance the efficacy of DC-based vaccines. We silencedTGF-β1 in L1210 cells with a  lentiviral shRNA vector and prepared the LEXTGF- β1si. It was shown that LEXTGF- β1si can significantly decrease TGF- β1 expression...
Source: Cancer Immunology, Immunotherapy - June 10, 2017 Category: Cancer & Oncology Source Type: research

Enhanced stimulation of human tumor-specific T cells by dendritic cells matured in the presence of interferon- γ and multiple toll-like receptor agonists
AbstractDendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought to establish a protocol to generate DC with greater immunostimulatory capacity. Immature DC were generated from healthy donor monocytes by culturing in the presence of IL-4 and GM-CSF and were further differentiated into mature DC by the addition of cocktails containing different cytokines and toll-like receptor (TLR) agonists. Overall, addition of IFN γ and the TLR7/8 agonist R848 during maturation was essenti...
Source: Cancer Immunology, Immunotherapy - June 10, 2017 Category: Cancer & Oncology Source Type: research

Endoplasmic reticulum stress regulates tumor growth and anti-tumor immunity: a promising opportunity for cancer immunotherapy
AbstractThe endoplasmic reticulum (ER) stress is a cellular process that occurs as a consequence of several stress circumstances, such as the accumulation of unfolded proteins in the lumen of the ER or distinct insults that disturb the ER normal function. Different conditions in the tumor microenvironment (TME), including hypoxia, nutrient deprivation, and the elevated production of reactive oxygen and nitrogen species destabilize the loading and dispatching of the newly synthesized proteins, triggering ER stress in cancer cells and tumor-infiltrating leukocytes. In order to cope with TME-induced ER stress, tumor and strom...
Source: Cancer Immunology, Immunotherapy - June 2, 2017 Category: Cancer & Oncology Source Type: research

In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells
AbstractAcute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Herein, we show that in vitro differentiation of cord blood CD34+ progenitors in the presence of aryl hydrocarbon receptor antagonists gives rise to clinically relevant numbers of pDC, as about 108 pDC can be produced from a typical cord blood unit. Blockin...
Source: Cancer Immunology, Immunotherapy - May 29, 2017 Category: Cancer & Oncology Source Type: research

Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy
AbstractThe importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described “vaccinal effect” exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expressi on) profile of peripheral blood T lymphocyte subsets (“conventional” CD4+ and CD8+, FOXP3+CD25bright Treg, and “innate-like...
Source: Cancer Immunology, Immunotherapy - May 29, 2017 Category: Cancer & Oncology Source Type: research

Professor Enrico Mihich, 1928 –2016
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 29, 2017 Category: Cancer & Oncology Source Type: research

CD45RA − Foxp3 high regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma
ConclusionCD45RA−Foxp3high Tregs are associated with the clinical course of HNSCC and might be a new target for treatment and an early marker of tumor recurrence in HNSCC patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 27, 2017 Category: Cancer & Oncology Source Type: research

Macrophage-derived interleukin-1beta promotes human breast cancer cell migration and lymphatic adhesion in vitro
This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1 β) in an in vitro model of LVI. IL-1β significantly augmented the adhesion and transmigration of breast cancer cell lines MCF7 and MDA-MB-231 across endothelial cell barriers. MDA-MB-231 and MCF7 showed a higher percentage of adhesion to lymphatic endothelial cells than blood endothelial cells fol lowing endothelial cell IL-1β stimulation (P 
Source: Cancer Immunology, Immunotherapy - May 27, 2017 Category: Cancer & Oncology Source Type: research

A gene polymorphism in PD-L1 promoter region is not associated with PD-L1 expression and patients ’ survival in gastric cancer
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 24, 2017 Category: Cancer & Oncology Source Type: research

Decreased human leukocyte antigen A*02:01 frequency is associated with risk of glioma and existence of human cytomegalovirus: a case –control study in Northern China
This study investigated the relationship between HLA distribution, presence of HCMV, and glioma development in a Han Chinese population.MethodsThe study population included 150 glioma patients and 150 tumor-free brain injury control subjects (control-A) matched according to geography, ethnicity, age, and gender. HLA allele frequency was compared between the two groups using peripheral blood samples by PCR sequence-based typing. These data were also compared with HLA frequencies obtained from a Northern Chinese Han population database (control-B). HCMV DNA was detected in the peripheral blood of glioma patients and control ...
Source: Cancer Immunology, Immunotherapy - May 18, 2017 Category: Cancer & Oncology Source Type: research

Paracrine release of IL-2 and anti-CTLA-4 enhances the ability of artificial polymer antigen-presenting cells to expand antigen-specific T cells and inhibit tumor growth in a mouse model
AbstractAccumulating evidence indicates that bead-based artificial antigen-presenting cells (aAPCs) are a powerful tool to induce antigen-specific T cell responses in vitro and in vivo. To date, most conventional aAPCs have been generated by coupling an antigen signal (signal 1) and one or two costimulatory signals, such as anti-CD28 with anti-LFA1 or anti-4-1BB (signal 2), onto the surfaces of cell-sized or nanoscale magnetic beads or polyester latex beads. The development of a biodegradable scaffold and the combined use of multiple costimulatory signals as well as third signals for putative clinical applications is the n...
Source: Cancer Immunology, Immunotherapy - May 13, 2017 Category: Cancer & Oncology Source Type: research

Common extracellular matrix regulation of myeloid cell activity in the bone marrow and tumor microenvironments
AbstractThe complex interaction between cells undergoing transformation and the various stromal and immunological cell components of the tumor microenvironment (TME) crucially influences cancer progression and diversification, as well as endowing clinical and prognostic significance. The immunosuppression characterizing the TME depends on the recruitment and activation of different cell types including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Less considered is the non-cellular component of the TME. Here, we focus on the extracellular matrix (ECM) regulatory activities that, w...
Source: Cancer Immunology, Immunotherapy - May 13, 2017 Category: Cancer & Oncology Source Type: research

Zoledronic acid renders human M1 and M2 macrophages susceptible to V δ2 + γδ T cell cytotoxicity in a perforin-dependent manner
In this study we focussed on macrophages (M ϕs), as these cells have been shown to take up ZA. We differentiated peripheral blood monocytes from healthy donors into Mϕs and then treated them with IFN-γ or IL-4 to generate M1 and M2 Mϕs, respectively. We characterised these Mϕs based on their phenotype and cytokine production and then te sted whether ZA rendered them susceptible to Vδ2+ T cell cytotoxicity. Consistent with the literature, IFN- γ-treated Mϕs expressed higher levels of the M1 markers CD64 and IL-12p70, whereas IL-4-treated Mϕs expressed higher levels of the M2 markers CD206 and ch...
Source: Cancer Immunology, Immunotherapy - May 13, 2017 Category: Cancer & Oncology Source Type: research

Dianthin-30 or gelonin versus monomethyl auristatin E, each configured with an anti-calcitonin receptor antibody, are differentially potent in vitro in high-grade glioma cell lines derived from glioblastoma
AbstractWe have reported that calcitonin receptor (CTR) is widely expressed in biopsies from the lethal brain tumourglioblastoma by malignant glioma and brain tumour-initiating cells (glioma stem cells) using anti-human CTR antibodies. A monoclonal antibody against an epitope within the extracellular domain of CTR was raised (mAb2C4) and chemically conjugated to either plant ribosome-inactivating proteins (RIPs) dianthin-30 or gelonin, or the drug monomethyl auristatin E (MMAE), and purified. In the high-grade glioma cell line (HGG, representing glioma stem cells) SB2b, in the presence of the triterpene glycoside SO1861, t...
Source: Cancer Immunology, Immunotherapy - May 13, 2017 Category: Cancer & Oncology Source Type: research

Expression of PD-L1 in keratoacanthoma and different stages of progression in cutaneous squamous cell carcinoma
AbstractBackgroundProgrammed cell death 1 (PD-1) and its ligands (PD-L1) play a major role in the immune responses of a variety of cancers.ObjectivesTo investigate the expression of PD-L1 in different progression forms of cutaneous squamous cell carcinoma (cSCC) and keratoacanthoma (KA).MethodsWe performed immunohistochemical staining of 21 KA, 26 actinic keratoses (AK), 20 Bowen ´s diseases (BD), and 26 high-risk cSCC. The staining patterns were assessed using the tumour proportion score and staining intensity evaluation. Immunohistology scores were statistically analysed.ResultsPD-L1 expression of tumour cells as w...
Source: Cancer Immunology, Immunotherapy - May 13, 2017 Category: Cancer & Oncology Source Type: research

Current status of chimeric antigen receptor engineered T cell-based and immune checkpoint blockade-based cancer immunotherapies
AbstractAdoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells (CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have lately shown remarkable success in certain tumor types. CAR-T cell-based therapies targeting CD19 can now induce durable remissions as well as prolong disease-free survival of patients with CD19 positive treatment refractory B cell malignancies and ICI-based therapies with humanized monoclonal antibodies against the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1 ligand, PD-L1, can now achieve durable remissions as well as prolongati...
Source: Cancer Immunology, Immunotherapy - May 11, 2017 Category: Cancer & Oncology Source Type: research

Intralesional interleukin-2 for unresectable mucosal melanoma refractory to nivolumab
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 11, 2017 Category: Cancer & Oncology Source Type: research

IDO, PTEN-expressing Tregs and control of antigen-presentation in the murine tumor microenvironment
AbstractThe tumor microenvironment is profoundly immunosuppressive. This creates a major barrier for attempts to combine immunotherapy with conventional chemotherapy or radiation, because the tumor antigens released by these cytotoxic agents are not cross-presented in an immunogenic fashion. In this Focused Research Review, we focus on mouse preclinical studies exploring the role of immunosuppressive Tregs expressing the PTEN lipid phosphatase, and the links between PTEN+ Tregs and the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO). IDO has received attention because it can be expressed by a variety of human tum...
Source: Cancer Immunology, Immunotherapy - May 9, 2017 Category: Cancer & Oncology Source Type: research

Cancer immunotherapy without frontiers: 2nd Annual Immuno-Oncology Meeting of the Centro de Investigaci ón de Cancer en Sonora (CICS), Ciudad Obregón, Sonora México, Dec 2–4, 2016
AbstractThis meeting in immuno-oncology brought together clinicians and scientists from United States, Canada, and M éxico with the goal of breaking down international walls and establishing new collaborations. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 8, 2017 Category: Cancer & Oncology Source Type: research

High prevalence of antibodies reacting to mimotopes of Simian virus 40 large T antigen, the oncoprotein, in serum samples of patients affected by non-Hodgkin lymphoma
This study allowed us to assay a new sera collection from non-Hodgkin lymphoma patients (NHL,n = 254). To verify the association between NHL and SV40 Tag, two totally independent cohorts were analysed: NHL1n = 150 and NHL2n = 104. The epidemiological survey included sera from HS1,n = 150; HS2,n = 104 and BC,n = 78. This new indirect ELISA revealed that antibodies against SV40 Tag mimotopes are detectable in NHL1 and NHL2 sera with a prevalence of 37 and 36%, respectively. The prevalence of SV40-antibodies detected in both NHL1 and NHL2 cohorts differs statisticall...
Source: Cancer Immunology, Immunotherapy - April 28, 2017 Category: Cancer & Oncology Source Type: research

KRAS mutation-induced upregulation of PD-L1 mediates immune escape in human lung adenocarcinoma
In this study, we investigated the correlation between PD-L1 expression and KRAS mutation and the functional significance of PD-1/PD-L1 blockade in KRAS-mutant lung adenocarcinoma. We found that PD-L1 expression was associated with KRAS mutation both in the human lung adenocarcinoma cell lines and tissues. PD-L1 was up-regulated by KRAS mutation through p-ERK but not p-AKT signaling. We also found that KRAS-mediated up-regulation of PD-L1 induced the apoptosis of CD3-positive T cells which was reversed by anti-PD-1 antibody (Pembrolizumab) or ERK inhibitor. PD-1 blocker or ERK inhibitor could recover the anti-tumor immunit...
Source: Cancer Immunology, Immunotherapy - April 27, 2017 Category: Cancer & Oncology Source Type: research

Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy
AbstractTumor-associated fibrosis is characterized by unchecked pro-fibrotic and pro-inflammatory signaling. The components of fibrosis including significant numbers of cancer-associated fibroblasts, dense collagen deposition, and extracellular matrix stiffness, are well appreciated regulators of tumor progression but may also be critical regulators of immune surveillance. While this suggests that the efficacy of immunotherapy may be limited in highly fibrotic cancers like pancreas, it also suggests a therapeutic opportunity to target fibrosis in these tumor types to reawaken anti-tumor immunity. This review discusses the ...
Source: Cancer Immunology, Immunotherapy - April 27, 2017 Category: Cancer & Oncology Source Type: research

HPV16 E7 DNA tattooing: safety, immunogenicity, and clinical response in patients with HPV-positive vulvar intraepithelial neoplasia
ConclusionDNA tattoo vaccination was shown to be safe. A low vaccine-induced immune response and no clinical response were observed in uVIN patients after TTFC-E7SH DNA tattoo vaccination. Therefore, a new phase I/II trial with an improved DNA vaccine format is currently in development for patients with uVIN. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 27, 2017 Category: Cancer & Oncology Source Type: research

The experience of immune checkpoint inhibitors in Chinese patients with metastatic melanoma: a retrospective case series
The objective response rates (ORRs) were 0, 25, and 20% for ipilimumab, pembrolizumab, and pembrolizumab plus ipilimumab, respectively. Pembrolizumab contained therapy was as effective in acral and mucosal melanoma patients (ORR 26.7 and 20%, respectively) as in non-acral cutaneous melanoma patients (ORR 26.7%). Baseline lactate dehydrogenase levels and relative lymphocyte counts were independent prognostic factors for PFS and OS. The incidences of grade 3 –4 adverse events were 14% in the two monotherapy groups and 30% in the combined therapy group. The most frequent adverse events were elevation of aminotransferase...
Source: Cancer Immunology, Immunotherapy - April 25, 2017 Category: Cancer & Oncology Source Type: research

FKBP51s signature in peripheral blood mononuclear cells of melanoma patients as a possible predictive factor for immunotherapy
In conclusion, FKBP51s-based immunophenotyping of melanoma patients revealed several profiles related to a negative immune regulatory control and identified an unknown Treg subset. These findings are likely to be useful in the selection of the patients that are candidate for immunothera py. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 22, 2017 Category: Cancer & Oncology Source Type: research

Downregulation of neuropilin-1 on macrophages modulates antibody-mediated tumoricidal activity
In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4+ T lymphocytes were significantly downregulated when peripheral blood mononuclear ce...
Source: Cancer Immunology, Immunotherapy - April 21, 2017 Category: Cancer & Oncology Source Type: research

MuPeXI: prediction of neo-epitopes from tumor sequencing data
AbstractPersonalization of immunotherapies such as cancer vaccines and adoptive T cell therapy depends on identification of patient-specific neo-epitopes that can be specifically targeted. MuPeXI, the mutant peptide extractor and informer, is a program to identify tumor-specific peptides and assess their potential to be neo-epitopes. The program input is a file with somatic mutation calls, a list of HLA types, and optionally a gene expression profile. The output is a table with all tumor-specific peptides derived from nucleotide substitutions, insertions, and deletions, along with comprehensive annotation, including HLA bi...
Source: Cancer Immunology, Immunotherapy - April 20, 2017 Category: Cancer & Oncology Source Type: research

The Summit for Cancer Immunotherapy (Summit4CI), June 26 –29, 2016 Halifax, Canada
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 13, 2017 Category: Cancer & Oncology Source Type: research

Can local radiotherapy and IL-12 synergise to overcome the immunosuppressive tumor microenvironment and allow “in situ tumor vaccination”?
AbstractThe abscopal effect, which is the spontaneous regression of tumors or metastases outside the radiation field, occurs rarely in cancer patients. Interestingly, radiotherapy (RT) triggers an immunogenic cell death (ICD) that is able to generate tumor-specific cytotoxic CD8+ T cells that are efficient in killing cancer cells. The key question is: why is this “abscopal effect” so uncommon in cancer patients treated with RT? Most probably, the main reason may be related to the highly immunosuppressive tumor microenvironment of well-established tumors that constantly antagonizes the anti-tumor immune response...
Source: Cancer Immunology, Immunotherapy - April 13, 2017 Category: Cancer & Oncology Source Type: research

Coexpressed modular gene expression reveals inverse correlation between immune responsive transcription and aggressiveness in gastric tumours
AbstractThe existing large number of gene expression profiles of tumour samples offers a great advantage for the integrative functional genomic exploration of molecular dysregulation in cancers. The clusters of genes (modules) derived from a gastric cancer (GC) coexpression network were explored to understand their clinical and functional significance. Among the modules derived from the GC mRNA expression network, six modules were relatively highly expressed in diffuse type gastric tumours. Elevated expression of genes related to extracellular matrix (ECM), angiogenesis, collagen and intracellular cytoskeletal components a...
Source: Cancer Immunology, Immunotherapy - April 12, 2017 Category: Cancer & Oncology Source Type: research

Prognostic implication of CD274 (PD-L1) protein expression in tumor-infiltrating immune cells for microsatellite unstable and stable colorectal cancer
In this study, we investigated the clinical relevance of CD274 (PD-L1) protein expression by tumor cells and tumor-infiltrating immune cells in colorectal cancer (CRC). To this end, 186 microsatellite instability-high (MSI-H) and 153 microsatellite stable (MSS) CRCs were subjected to immunohistochemistry (IHC) analysis for the expression of CD274 and mismatch repair proteins. CD274 expression was evaluated in tumor cells at the center (TC) and periphery (TP), and immune cells at the center (IC) and periphery (IP) of CRC. IHC slides stained for CD3 and CD8 were scanned using an Aperio ScanScope for precise calculation of tu...
Source: Cancer Immunology, Immunotherapy - April 12, 2017 Category: Cancer & Oncology Source Type: research

Tumor-associated myeloid cells as guiding forces of cancer cell stemness
AbstractDue to their ability to differentiate into various cell types and to support tissue regeneration, stem cells simultaneously became the holy grail of regenerative medicine and the evil obstacle in cancer therapy. Several studies have investigated niche-related conditions that favor stemness properties and increasingly emphasized their association with an inflammatory environment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are major orchestrators of cancer-related inflammation, able to dynamically express different polarized inflammatory programs that promote tumor outgrowth, inc...
Source: Cancer Immunology, Immunotherapy - April 11, 2017 Category: Cancer & Oncology Source Type: research

IDO and galectin-3 hamper the ex vivo generation of clinical grade tumor-specific T cells for adoptive cell therapy in metastatic melanoma
AbstractAdoptive T cell transfer (ACT) with ex vivo-expanded tumor-reactive T cells proved to be successful for the treatment of metastatic melanoma patients. Mixed lymphocyte tumor cell cultures (MLTC) can be used to generate tumor-specific T cells for ACT; however, in a number of cases tumor-reactive T cell, expansion is far from optimal. We hypothesized that this is due to tumor intrinsic and extrinsic factors and aimed to identify and manipulate these factors so to optimize our clinical, GMP-compliant MLTC protocol. We found that the tumor cell produced IDO and/or galectin-3, and the accumulation of CD4+CD25hiFoxP3+ T ...
Source: Cancer Immunology, Immunotherapy - April 11, 2017 Category: Cancer & Oncology Source Type: research

Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer
AbstractIn newly diagnosed metastatic hormone-naive prostate cancer (mPC), telomerase-based immunotherapy with the novel hTERT peptide vaccine UV1 can induce immune responses with potential clinical benefit. This phase I dose escalation study of UV1 evaluated safety, immune response, effects on prostate-specific antigen (PSA) levels, and preliminary clinical outcome. Twenty-two patients with newly diagnosed metastatic hormone-na ïve PC (mPC) were enrolled; all had started androgen deprivation therapy and had no visceral metastases. Bone metastases were present in 17 (77%) patients and 16 (73%) patients had affected ly...
Source: Cancer Immunology, Immunotherapy - April 8, 2017 Category: Cancer & Oncology Source Type: research

Genetic evolution of uveal melanoma guides the development of an inflammatory microenvironment
AbstractUveal melanoma (UM) is characterized by a number of genetic aberrations that follow a certain chronology and are tightly linked to tumor recurrence and survival. Loss of chromosome 3, bi-allelic loss of BAP1 expression, and gain in chromosome 8q have been associated with metastasis formation and death, while loss of chromosome 3 has been associated with the influx of macrophages and T cells. We used a set of genetically-classified UM to study immune infiltration in the context of their genetic evolution. We show in two independent cohorts that lack of BAP1 expression is associated with an increased density of CD3+ ...
Source: Cancer Immunology, Immunotherapy - April 8, 2017 Category: Cancer & Oncology Source Type: research

CCR5 in recruitment and activation of myeloid-derived suppressor cells in melanoma
AbstractMalignant melanoma is characterized by the development of chronic inflammation in the tumor microenvironment, leading to the accumulation of myeloid-derived suppressor cells (MDSCs). Usingret transgenic mouse melanoma model, we found a significant migration of MDSCs expressing C-C chemokine receptor (CCR)5 into primary tumors and metastatic lymph nodes, which was correlated with tumor progression. An increased CCR5 expression on MDSCs was associated with elevated concentrations of CCR5 ligands in melanoma microenvironment.In vitro experiments showed that the upregulation of CCR5 expression on CD11b+Gr1+ immature my...
Source: Cancer Immunology, Immunotherapy - April 5, 2017 Category: Cancer & Oncology Source Type: research

Bone marrow myeloid cells in regulation of multiple myeloma progression
AbstractSurvival, growth, and response to chemotherapy of cancer cells depends strongly on the interaction of cancer cells with the tumor microenvironment. In multiple myeloma, a cancer of plasma cells that localizes preferentially in the bone marrow, the microenvironment is highly enriched with myeloid cells. The majority of myeloid cells are represented by mature and immature neutrophils. The contribution of the different myeloid cell populations to tumor progression and chemoresistance in multiple myeloma is discussed. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 4, 2017 Category: Cancer & Oncology Source Type: research

Cancer immunotherapy: how low-level ionizing radiation can play a key role
AbstractThe cancer immunoediting hypothesis assumes that the immune system guards the host against the incipient cancer, but also “edits” the immunogenicity of surviving neoplastic cells and supports remodeling of tumor microenvironment towards an immunosuppressive and pro-neoplastic state. Local irradiation of tumors during standard radiotherapy, by killing neoplastic cells and generating inflammation, stimulates anti-can cer immunity and/or partially reverses cancer-promoting immunosuppression. These effects are induced by moderate (0.1–2.0 Gy) or high (>2  Gy) doses of ionizing radiation w...
Source: Cancer Immunology, Immunotherapy - March 30, 2017 Category: Cancer & Oncology Source Type: research

Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy
AbstractNasal natural killer/T-cell lymphoma (NNKTL) is an aggressive neoplasm with poor therapeutic responses and prognosis. The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway plays an important role in immune evasion of tumor cells through T-cell exhaustion. The aim of the present study was to examine the expression of PD-L1 and PD-1 molecules in NNKTL. We detected the expression of PD-L1 in biopsy samples from all of the NNKTL patients studied. PD-L1 was found on both malignant cells and tumor-infiltrating macrophages, while PD-1-positive mononuclear cells infiltrated the tumor tissues in 36% of patie...
Source: Cancer Immunology, Immunotherapy - March 27, 2017 Category: Cancer & Oncology Source Type: research

PD-L1 overexpression is partially regulated by EGFR/HER2 signaling and associated with poor prognosis in patients with non-small-cell lung cancer
AbstractImmunocheckpoint inhibitors targeting the programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) axis have shown promising results in patients with non-small-cell lung cancer (NSCLC). Recent research has shown that epidermal growth factor receptor (EGFR) signaling affects PD-L1 expression in NSCLC cells; however, the mechanism regulating PD-L1 expression in tumor cells remains unclear. Using immunohistochemistry, we evaluated the impact of expression of PD-L1 and EGF family receptors EGFR and human epidermal growth factor receptor 2 (HER2) in tumor cells from 91 patients with pathological Stage IA –IIIA NSC...
Source: Cancer Immunology, Immunotherapy - March 25, 2017 Category: Cancer & Oncology Source Type: research