The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma
ConclusionsOur findings indicate that sPD-1 and sPD-L1 are independent prognostic factors with opposite prognostic roles in predicting both DFS and OS in HCC patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - December 1, 2018 Category: Cancer & Oncology Source Type: research

Tumor-infiltrating immune cell subpopulations and programmed death ligand 1 (PD-L1) expression associated with clinicopathological and prognostic parameters in ependymoma
This study showed that the analysis of tumor-infiltrating immune cells could aid in predicting the prognosis of ependymoma patients and in determining therapeutic strategies to target the tumor microenvironment. PD-L1 expression in the ST-RELA subgroup suggests that this marker has a potential added value for future immunotherapy treatments. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - November 27, 2018 Category: Cancer & Oncology Source Type: research

Can benign lymphoid tissue changes in 18 F-FDG PET/CT predict response to immunotherapy in metastatic melanoma?
ConclusionBased on our findings, 10% patients in the interim or late PET/CT showed ‘sarcoid-like lymphadenopathy’ as response to treatment. All these patients showed disease control, implying a relation between the appearance of sarcoid-like lymphadenopathy and the clinical benefit of anti-CTLA-4 therapy. On the other hand, quantitative18F-FDG PET analysis of the spleen showed a poor performance in predicting clinical benefit to ipilimumab. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - November 26, 2018 Category: Cancer & Oncology Source Type: research

An alphavirus-based therapeutic cancer vaccine: from design to clinical trial
AbstractCancer immunotherapy has greatly advanced in recent years. Most immunotherapeutic strategies are based on the use of immune checkpoint blockade to unleash antitumor immune responses or on the induction or adoptive transfer of immune effector cells. We aim to develop therapeutic vaccines based on recombinant Semliki Forest virus vectors to induce tumor-specific effector immune cells. In this review, we describe our ongoing work on SFV-based vaccines targeted against human papillomavirus- and hepatitis C virus-related infections and malignancies, focusing on design, delivery, combination strategies, preclinical effic...
Source: Cancer Immunology, Immunotherapy - November 21, 2018 Category: Cancer & Oncology Source Type: research

Upregulation of tumor PD-L1 by neoadjuvant chemoradiotherapy (neoCRT) confers improved survival in patients with lymph node metastasis of locally advanced rectal cancers
In this study, we examined the roles of tumor PD-L1 and IFN-γ before and after neoCRT in locally advanced rectal cancer (LARC) patients. Our results demonstrate that patients with high PD-L1 expression in post-neoCRT tissues exhibit improved 5-year disease-free survival (DFS) and overall survival (OS) compared with those with low PD-L1 e xpression (p 
Source: Cancer Immunology, Immunotherapy - November 17, 2018 Category: Cancer & Oncology Source Type: research

A phase I clinical study of a cocktail vaccine of Wilms ’ tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma
ConclusionThe safety of a cocktail vaccine of WT1 HLA class I and II peptides for malignant gliomas was verified. This vaccine is, therefore, considered promising for patients with recurrent malignant glioma. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - November 14, 2018 Category: Cancer & Oncology Source Type: research

Targeting the polarization of tumor-associated macrophages and modulating mir-155 expression might be a new approach to treat diffuse large B-cell lymphoma of the elderly
This study aims to evaluate the relationship between macrophage polarization pattern in the tumor microenvironment and relative expression of miR-155 in EBV + DLBCLe and EBV-negative DLBCL patients. We studied 28 EBV + DLBCLe and 65 EBV-negative DLBCL patient s. Tumor-associated macrophages (TAM) were evaluated by expression of CD68, CD163 and CD163/CD68 ratio (degree of M2 polarization), using tissue microarray. RNA was extracted from paraffin-embedded tumor samples for miR-155 relative expression study. We found a significantly higher CD163/CD68 ratio in EBV + DLBCLe compared to ...
Source: Cancer Immunology, Immunotherapy - November 14, 2018 Category: Cancer & Oncology Source Type: research

Phase 1 study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell carcinoma
In conclusion, the optimal Treg depleting dose and schedule of CTX, when combined with everolimus, is 50 mg once daily. This combination leads to acceptable adverse events in comparison with everolimus alone. Currently, the here selected combin ation is being evaluated in a phase II clinical trial.Trial registrationNCT01462214. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - November 9, 2018 Category: Cancer & Oncology Source Type: research

Apoptosis of tumor-infiltrating T lymphocytes: a new immune checkpoint mechanism
AbstractImmunotherapy based on checkpoint inhibitors is providing substantial clinical benefit, but only to a minority of cancer patients. The current priority is to understand why the majority of patients fail to respond. Besides T-cell dysfunction, T-cell apoptosis was reported in several recent studies as a relevant mechanism of tumoral immune resistance. Several death receptors (Fas, DR3, DR4, DR5, TNFR1) can trigger apoptosis when activated by their respective ligands. In this review, we discuss the immunomodulatory role of the main death receptors and how these are shaping the tumor microenvironment, with a focus on ...
Source: Cancer Immunology, Immunotherapy - November 7, 2018 Category: Cancer & Oncology Source Type: research

The nature of the human T cell response to the cancer antigen 5T4 is determined by the balance of regulatory and inflammatory T cells of the same antigen-specificity: implications for vaccine design
This study mapped the fine specificity of Th1 and Treg cell responses to the 5T4 protein. Surprisingly, both immunogenic peptides and those recognised by Tregs clustered in the same HLA-DR transcending epitope-rich hotspots within the 5T4 protein. Similarly, regions of low Th1-cell immunogenicity also did not contain peptides capable of stimulating Tregs, further supporting the notion that Treg and Th1 cells recognise the same peptides. Understanding the rules which govern the balance of Th1 and Treg cells responding to a given peptide specificity is, therefore, of fundamental importance to designing strategies for manipul...
Source: Cancer Immunology, Immunotherapy - November 7, 2018 Category: Cancer & Oncology Source Type: research

Hyperresponsiveness to interferon gamma exposure as a response mechanism to anti-PD-1 therapy in microsatellite instability colorectal cancer
In this study, enhanced PD-L1 expression increased survival in CT26 cells, and PD-1 blockade increased the CTL profile and apoptotic cells in mice with CRC. Our in vitro findings showed that PD-L1 expression was significantly upregulated by a low-dose IFNγ treatment, and the MSI-H cell line might exhibit hyperresponsiveness to IFNγ exposure partly through the JAK–STAT pathway. These results suggest that intrinsic PD-L1 in co operation with extrinsic IFNγ exposure in CRC may be more responsive to anti-PD-1 therapy, mainly through the CTL profile in the tumor microenvironment. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - November 7, 2018 Category: Cancer & Oncology Source Type: research

Targeting CTCFL/BORIS for the immunotherapy of cancer
AbstractCancer vaccines have great potential in the fight against metastatic malignancies. Current anti-tumor immunotherapy is hindered by existing tolerance to tumor-associated antigens (TAA) and tumor escape using various mechanisms, highlighting the need for improved targets for immunotherapy. The cancer –testis antigen CTCFL/BORIS was discovered 16 years ago and possesses all features necessary for an ideal TAA. Recently CTCFL/BORIS has received additional attention as a target expressed in cancer stem cells (CSC). These cells drive tumor growth recurrence, metastasis, and treatment resistance. CTCFL/BORIS s...
Source: Cancer Immunology, Immunotherapy - November 2, 2018 Category: Cancer & Oncology Source Type: research

Development of CDX-1140, an agonist CD40 antibody for cancer immunotherapy
AbstractLimitations of immunotherapy include poorly functioning events early in the immune response cycle, such as efficient antigen presentation and T cell priming. CD40 signaling in dendritic cells leads to upregulation of cell surface costimulatory and MHC molecules and the generation of cytokines, which promotes effective priming of CD8+ effector T cells while minimizing T cell anergy and the generation of regulatory T cells. This naturally occurs through interaction with CD40 ligand (CD40L) expressed on CD4+ T-helper cells. CD40 signaling can also be achieved using specific antibodies, leading to several agonist CD40 ...
Source: Cancer Immunology, Immunotherapy - October 31, 2018 Category: Cancer & Oncology Source Type: research

Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma
ConclusionsAn immune profile driven by CD103+ TIL content, alone and in combination with CD4+ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 25, 2018 Category: Cancer & Oncology Source Type: research

Stromal interleukin-33 promotes regulatory T cell-mediated immunosuppression in head and neck squamous cell carcinoma and correlates with poor prognosis
In this study, we examined IL-33+ and Foxp3+ cells by immunohistochemistry in 68 laryngeal squamous cell cancer patients, followed by functional analysis of IL-33 in Tregs. In addition, the suppressive function of Tregs was assessed by cell proliferation assays. The level of stromal IL-33 was significantly upregulated in advanced versus early stage HNSCC patients and positively correlated with Foxp3+ Treg infiltration as well as a poor prognosis. ST2 is regarded as the only receptor of IL-33. Infiltrated ST2-expressing Tregs were responsive to IL-33, and the percentage of Tregs was increased upon IL-33 stimulation. Functio...
Source: Cancer Immunology, Immunotherapy - October 25, 2018 Category: Cancer & Oncology Source Type: research

Inhibitory functions of PD-L1 and PD-L2 in the regulation of anti-tumor immunity in murine tumor microenvironment
AbstractAlthough a role of PD-L1 in the suppression of anti-tumor immunity and its value as a predictive biomarker has been suggested by various preclinical and clinical studies, the  precise mechanisms how PD-L1 and PD-L2, another ligand of PD-1, regulate anti-tumor immunity in the tumor microenvironment are yet to be fully explored. Here, we address this issue using PD-L1-deficient tumor cells, PD-L1-knockout (KO) mice, anti-PD-L1 monoclonal antibody (mAb), and anti-PD-L2 mAb . Firstly, PD-L1-deficient or competent tumor cells were inoculated into wild-type or PD-L1-KO mice. Results of tumor growth and mouse surviva...
Source: Cancer Immunology, Immunotherapy - October 24, 2018 Category: Cancer & Oncology Source Type: research

Role of myeloid regulatory cells (MRCs) in maintaining tissue homeostasis and promoting tolerance in autoimmunity, inflammatory disease and transplantation
AbstractMyeloid cells play a pivotal role in regulating innate and adaptive immune responses. In inflammation, autoimmunity, and after transplantation, myeloid cells have contrasting roles: on the one hand they initiate the immune response, promoting activation and expansion of effector T-cells, and on the other, they counter-regulate inflammation, maintain tissue homeostasis, and promote tolerance. The latter activities are mediated by several myeloid cells including polymorphonuclear neutrophils, macrophages, myeloid-derived suppressor cells, and dendritic cells. Since these cells have been associated with immune suppres...
Source: Cancer Immunology, Immunotherapy - October 24, 2018 Category: Cancer & Oncology Source Type: research

INT-HA induces M2-like macrophage differentiation of human monocytes via TLR4-miR-935 pathway
AbstractAs a major component of the microenvironment of solid tumors, tumor-associated macrophages (TAMs) facilitate tumor progression. Intermediate-sized hyaluronan (INT-HA) fragments have an immunological function in cell differentiation; however, their role in promoting the polarization of non-activated macrophages to an M2-like TAM phenotype has not been characterized, and the underlying mechanisms remain unclear. Here, we used a miRNA microarray to find that some miRNAs (especially miR-935) were differentially regulated in INT-HA-induced M2-like macrophages. According to RT-qPCR and Western blot, there was an associat...
Source: Cancer Immunology, Immunotherapy - October 19, 2018 Category: Cancer & Oncology Source Type: research

The expression of MHC class II molecules on murine breast tumors delays T-cell exhaustion, expands the T-cell repertoire, and slows tumor growth
AbstractThe expression of MHC class II molecules (MHCII) on tumor cells correlates with survival and responsiveness to immunotherapy. However, the mechanisms underlying these observations are poorly defined. Using a murine breast tumor line, we showed that MHCII-expressing tumors grew more slowly than controls and recruited more functional CD4+ and CD8+ T cells. In addition, MHCII-expressing tumors contained more TCR clonotypes expanded to a larger degree than control tumors. Functional CD8+ T cells in tumors depended on CD4+ T cells. However, both CD4+ and CD8+ T cells eventually became exhausted, even in MHCII-expressing...
Source: Cancer Immunology, Immunotherapy - October 17, 2018 Category: Cancer & Oncology Source Type: research

Histamine targets myeloid-derived suppressor cells and improves the anti-tumor efficacy of PD-1/PD-L1 checkpoint blockade
AbstractMyeloid-derived suppressor cells (MDSCs) are immature monocytes and granulocytes that impede immune-mediated clearance of malignant cells by multiple mechanisms, including the formation of immunosuppressive reactive oxygen species (ROS) via the myeloid cell NADPH oxidase (NOX2). Histamine dihydrochloride (HDC), a NOX2 inhibitor, exerts anti-cancer efficacy in experimental tumor models but the detailed mechanisms are insufficiently understood. To determine effects of HDC on the MDSC compartment we utilized three murine cancer models known to entail accumulation of MDSC, i.e. EL-4 lymphoma, MC-38 colorectal carcinoma...
Source: Cancer Immunology, Immunotherapy - October 12, 2018 Category: Cancer & Oncology Source Type: research

Association of IL-36 γ with tertiary lymphoid structures and inflammatory immune infiltrates in human colorectal cancer
AbstractIL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36 γ is an IL-1 family cytokine involved in polarizing type-1 immune responses. However, its function in the gut, including in colorectal cancer pathogenesis, is not well appreciated. In a murine model of colon carcinoma, IL-36γ controls tertiary lymphoid structure formation and promotes a type-1 imm une response concurrently with a decrease in expression of immune checkpoint molecules in the tumor microenvironment. Here, we demonstrate that IL-36γ plays a simil...
Source: Cancer Immunology, Immunotherapy - October 12, 2018 Category: Cancer & Oncology Source Type: research

Soluble CTLA-4 as a favorable predictive biomarker in metastatic melanoma patients treated with ipilimumab: an Italian melanoma intergroup study
In conclusion, our results suggest that high sCTLA-4 serum levels might predict favorable clinical outcome and higher risk of irAEs in IPI-treated MM patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 11, 2018 Category: Cancer & Oncology Source Type: research

Recurrent grade 4 panuveitis with serous retinal detachment related to nivolumab treatment in a patient with metastatic renal cell carcinoma
AbstractBlockade of programmed cell death-1 (PD-1) has become one of the most promising immunotherapies for many human cancers. However, immune-related adverse events can be produced by anti-PD-1 therapy. Uveitis is a rare but potentially devastating side effect of anti-PD-1 therapy. Delay in diagnosis or improper treatment may eventually lead to irreversible blindness. Therefore, it is important for the oncologist and the ophthalmologist to recognize and manage this adverse event properly in patients receiving anti-PD-1 therapy in a timely manner. Here we present a grade 4 panuveitis with bilateral serous retinal detachme...
Source: Cancer Immunology, Immunotherapy - October 11, 2018 Category: Cancer & Oncology Source Type: research

Phase I/II clinical trial of a Wilms ’ tumor 1-targeted dendritic cell vaccination-based immunotherapy in patients with advanced cancer
AbstractDendritic cell (DC)-based immunotherapies have been created for a broad expanse of cancers, and DC vaccines prepared with Wilms ’ tumor protein 1 (WT1) peptides have shown great therapeutic efficacy in these diseases. In this paper, we report the results of a phase I/II study of a DC-based vaccination for advanced breast, ovarian, and gastric cancers, and we offer evidence that patients can be effectively vaccinated with a utologous DCs pulsed with WT1 peptide. There were ten patients who took part in this clinical study; they were treated biweekly with a WT1 peptide-pulsed DC vaccination, with toxicity and c...
Source: Cancer Immunology, Immunotherapy - October 10, 2018 Category: Cancer & Oncology Source Type: research

Opposing roles of eosinophils in cancer
AbstractEosinophils are a subset of granulocytes mostly known for their ability to combat parasites and induce allergy. Although they were described to be related to cancer more than 100  years ago, their role in tumors is still undefined. Recent observations revealed that they display regulatory functions towards other immune cell subsets in the tumor microenvironment or direct cytotoxic functions against tumor cells, leading to either antitumor or protumor effects. This paradoxic al role of eosinophils was suggested to be dependent on the different factors in the TME. In addition, the clinical relevance of these cel...
Source: Cancer Immunology, Immunotherapy - October 9, 2018 Category: Cancer & Oncology Source Type: research

Prediction of neoepitopes from murine sequencing data
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 5, 2018 Category: Cancer & Oncology Source Type: research

An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells
AbstractBreast cancer remains one of the leading causes of cancer-associated death worldwide. Conventional treatment is associated with substantial toxicity and suboptimal efficacy. We, therefore, developed and evaluated the in vitro efficacy of an autologous dendritic cell (DC) vaccine to treat breast cancer. We recruited 12 female patients with stage 1, 2, or 3 breast cancer and matured their DCs with autologous tumour-specific lysate, a toll-like receptor (TLR)-3 and 7/8 agonist, and an interferon-containing cocktail. The efficacy of the vaccine was evaluated by its ability to elicit a cytotoxic T-lymphocyte response to...
Source: Cancer Immunology, Immunotherapy - October 3, 2018 Category: Cancer & Oncology Source Type: research

Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics
AbstractBreast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23 α, miR-146α, miR-155 and miR-181α), in opera...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Epidermal growth factor receptor peptide vaccination induces cross-reactive immunity to human EGFR, HER2, and HER3
AbstractCurrent treatments for tumors expressing epidermal growth factor receptor (EGFR) include anti-EGFR monoclonal antibodies, often used in conjunction with the standard chemotherapy, radiation therapy, or other EGFR inhibitors. While monoclonal antibody treatment is efficacious in many patients, drawbacks include its high cost of treatment and side effects associated with multiple drug infusions. As an alternative to monoclonal antibody treatments, we have focused on peptide-based vaccination to trigger natural anti-tumor antibodies. Here, we demonstrate that peptides based on a region of the EGFR extracellular domain...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia
AbstractIn elderly acute myeloid leukemia (AML) patients post-remission treatment options are associated with high comorbidity rates and poor survival. Dendritic cell (DC)-based immunotherapy is a promising alternative treatment strategy. A novel allogeneic DC vaccine, DCP-001, was developed from an AML-derived cell line that uniquely combines the positive features of allogeneic DC vaccines and expression of multi-leukemia-associated antigens. Here, we present data from a phase I study conducted with DCP-001 in 12 advanced-stage elderly AML patients. Patients enrolled were in complete remission (CR1/CR2) (n =&thinsp...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Fusobacterium nucleatum promotes M2 polarization of macrophages in the microenvironment of colorectal tumours via a TLR4-dependent mechanism
AbstractFusobacterium nucleatum (Fn) has been shown to promote colorectal cancer (CRC) development by inhibiting host anti-tumour immunity. However, the impact ofFn infection on macrophage polarization and subsequent intestinal tumour formation as well as the underlying molecular pathways has not been investigated. We investigated the impact ofFn infection on macrophage polarization in human CRCs and cultured macrophages as well as the effects on macrophage phenotype and intestinal tumour formation inApcMin/+ mice. We also examined whether macrophage-polarized activation challenged byFn infection via a TLR4-dependent mecha...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Increased antitumor activities of glypican-3-specific chimeric antigen receptor-modified T cells by coexpression of a soluble PD1 –CH3 fusion protein
AbstractOur recent clinical study demonstrated that glypican-3 (GPC3)-specific chimeric antigen receptor-modified T (CAR-T) cells are a promising treatment for hepatocellular carcinoma (HCC). However, the interaction of programmed cell death 1 (PD-1) and PD-L1-mediated T-cell inhibition is involved in immune evasion in a wide range of solid tumors, including HCC. To overcome this problem, we introduced a fusion protein composed of a PD-1 extracellular domain and CH3 from IgG4 into GPC3-specific CAR-T cells (GPC3-28Z) to block the PD-1/PD-L1 pathway. GPC3-specific CAR-T cells carrying the PD-1 –CH3 fusion protein (sPD...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

High-grade glioma associated immunosuppression does not prevent immune responses induced by therapeutic vaccines in combination with T reg depletion
AbstractHigh-grade gliomas (HGG) exert systemic immunosuppression, which is of particular importance as immunotherapeutic strategies such as therapeutic vaccines are increasingly used to treat HGGs. In a first cohort of 61 HGG patients we evaluated a panel of 30 hematological and 34 plasma biomarkers. Then, we investigated in a second cohort of 11 relapsed HGG patients receiving immunomodulation with metronomic cyclophosphamide upfront to a DC-based vaccine whether immune abnormalities persisted and whether they hampered induction of IFN γ+ T-cell responses. HGG patients from the first cohort showed increased numbers...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Pilot trial of the hu14.18-IL2 immunocytokine in patients with completely resectable recurrent stage III or stage IV melanoma
AbstractPhase I testing of the hu14.18-IL2 immunocytokine (IC) in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5  mg/m2/day. Preclinical data in IC-treated tumor-bearing mice with low tumor burden documented striking antitumor effects. Patients with completely resectable recurrent stage III or stage IV melanoma were scheduled to receive 3 courses of IC at 6  mg/m2/day i.v. on days 1, 2 and 3 of each 28-day course. Patients were randomized to complete surgical resection either following neoadjuvant (Group A) or prior to adjuvant (Group B) IC course 1. Primary...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

3-Day monocyte-derived dendritic cells stimulated with a combination of OK432, TLR7/8 ligand, and prostaglandin E 2 are a promising alternative for cancer immunotherapy
In conclusion, the OK432 cocktail has the advantage of inducing IL-12p70 production without impairing phenotype or T-cell stimulatory capacity of the cells and might, therefore, be an advantageous alternative to be used in DC-based immunotherapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Ex vivo expanded tumour-infiltrating lymphocytes from ovarian cancer patients release anti-tumour cytokines in response to autologous primary ovarian cancer cells
AbstractEpithelial ovarian cancer (EOC) is the leading cause of gynaecological cancer-related death in Europe. Although most patients achieve an initial complete response with first-line treatment, recurrence occurs in more than 80% of cases. Thus, there is a clear unmet need for novel second-line treatments. EOC is frequently infiltrated with T lymphocytes, the presence of which has been shown to be associated with improved clinical outcomes. Adoptive T-cell therapy (ACT) using ex vivo-expanded tumour-infiltrating lymphocytes (TILs) has shown remarkable efficacy in other immunogenic tumours, and may represent a promising ...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics
AbstractBreast cancer (BCa) is a heterogeneous disease with different histological, prognostic and clinical aspects. Therefore, the need for identification of novel biomarkers for diagnosis, prognosis and monitoring of disease, as well as treatment outcome prediction remains at the forefront of research. The search for circulating elements, obtainable by simple peripheral blood withdrawal, which may serve as possible biomarkers, constitutes still a challenge. In the present study, we have evaluated the expression of 6 circulating miRNAs, (miR-16, miR-21, miR-23 α, miR-146α, miR-155 and miR-181α), in opera...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Absence of host NF- κB p50 induces murine glioblastoma tumor regression, increases survival, and decreases T-cell induction of tumor-associated macrophage M2 polarization
AbstractHigh-grade gliomas harbor abundant myeloid cells that suppress anti-tumor immunity and support tumor growth. Targeting transcription factors, such as NF- κB p50, that mediate suppressive myeloid M2 polarization may prove therapeutic. GL261-Luc glioblastoma cells were inoculated into wild-type and p50−/− mice, followed by analysis of tumor growth, survival, tumor myeloid cells, and T cells. The absence of host p50 slows tumor growth and enables regression in 30% of recipients, leading to prolonged survival. Tumors developing in p50−/− mice possess a greater concentration of tumor-infilt...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Regulatory mechanisms of PD-L1 expression in cancer cells
AbstractImmunotherapy targeting the PD-L1/PD-1 pathway using antibodies is effective in the clinical treatment of a multitude of cancers. This makes research of the regulatory mechanisms of PD-1 expression in cancer cells intriguing. PD-L1 expression can be categorized into inducible expression, attributed to extrinsic factors in the microenvironment, and constitutive expression, attributed to intrinsic cancer-driving gene alteration. The mechanisms of PD-L1 expression in cancer cells operate at multiple levels, including gene amplification, chromatin modification, transcription, posttranscription, translation and posttran...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Antitumor virotherapy using syngeneic or allogeneic mesenchymal stem cell carriers induces systemic immune response and intratumoral leukocyte infiltration in mice
In this study we use our virotherapy Celyvir with syngeneic and allogeneic mouse mesenchymal stem cells to determine their antitumor efficacy in a C57BL/6 murine adenocarcinoma model. Adoptive transfer of splenocytes from treated mice to new tumor-bearing mice followed by a secondary adoptive transfer to a third group was performed. Similar reduction of tumor growth and systemic activation of the innate and adaptive immune system was observed in groups treated with syngeneic or allogeneic mesenchymal stem cells loaded with ICOVIR-5. Moreover, a different pattern of infiltration was observed by immunofluorescence in Celyvir...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Safety and immunogenicity of a potential checkpoint blockade vaccine for canine melanoma
In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8+ and CD4+ T cells secreting interferon-(IFN)-...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Case report: Long-term survival of a pancreatic cancer patient immunized with an SVN-2B peptide vaccine
AbstractA 62-year-old woman who underwent surgery to treat pancreatic cancer provided written, informed consent to undergo adjuvant therapy with gemcitabine, tegafur, and uracil. However, this was stopped after only 14  days due to Grade 4 neutropenia. She was then started on vaccine therapy with Survivin 2B peptide (SVN-2B) including IFA and INF-α. Although metastatic lung tumors were identified and resected at 82 months after surgery, the patient has remained free of new or relapsed disease for 12 years ther eafter. Tetramer and ELISPOT assays revealed the continuous circulation of SVN-2B-restricted ...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells
AbstractCholangiocarcinoma (CCA) is a cancer of the bile ducts that is associated with poor prognosis and poor treatment outcome. Approximately one-third of CCA patients can undergo surgery, but the recurrence rate is high and chemotherapy often cannot satisfactorily prolong survival. Cellular immunotherapy based on adoptive T-cell transfer is a potential treatment for CCA; however, the development of this technology and the search for an appropriate tumor-associated antigen are still ongoing. To enhance the cytotoxic activity of effector T cells against CCA, we developed self-differentiated monocyte-derived dendritic cell...
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study
ConclusionsOur study suggests that immunotherapy is effective and well tolerated in the elderly. The PFS on pembrolizumab was greater than expected, a finding that needs to be investigated further. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 1, 2018 Category: Cancer & Oncology Source Type: research

CD19 + tumor-infiltrating B-cells prime CD4 + T-cell immunity and predict platinum-based chemotherapy efficacy in muscle-invasive bladder cancer
ConclusionCD19+ TIB was identified as an independent prognostic factor, which could predict for post-surgery survival and platinum-based ACT benefits in MIBC. CD19+ TIB serve as antigen-presenting cells (APCs) to activate CD4+ TIT in the tumor environment of MIBC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 26, 2018 Category: Cancer & Oncology Source Type: research

TRPM2 modulates neutrophil attraction to murine tumor cells by regulating CXCL2 expression
AbstractIn recent years, immune cells were shown to play critical roles in tumor growth and metastatic progression. In this context, neutrophils were shown to possess both pro- and anti-tumor properties. To exert their anti-tumor effect, neutrophils need to migrate towards, and form physical contact with tumor cells. Neutrophils secrete H2O2 in a contact-dependent mechanism, thereby inducing a lethal Ca2+ influx via the activation of the H2O2-dependent TRPM2 Ca2+ channel. Here, we explored the mechanism regulating neutrophil chemoattraction to tumor cells. Interestingly, we found that TRPM2 plays a role in this context as ...
Source: Cancer Immunology, Immunotherapy - September 24, 2018 Category: Cancer & Oncology Source Type: research

The role of CCR5 in directing the mobilization and biological function of CD11b + Gr1 + Ly6C low polymorphonuclear myeloid cells in cancer
AbstractBone marrow (BM) cells of the hematopoietic system, also known as BM-derived leukocytes (BMD), are mobilized from the BM to the blood and then colonize tumor sites. These cells then become key players in either promoting or regulating the development and progression of tumors. Among the cells that suppress anti-tumor immunity are regulatory T cells (Tregs), tumor-associated macrophages (TAMS) and myeloid-derived suppressor cells (MDSC). MDSC comprise CD11b+Gr1+Ly6Clow polymorphonuclear myeloid cells (PMN-MDSC), and CD11b+Gr1+Ly6Chigh monocytic myeloid cells (Mo-MDSC). Several studies including ours have identified ...
Source: Cancer Immunology, Immunotherapy - September 19, 2018 Category: Cancer & Oncology Source Type: research