Expression profiles and function of IL6 in polymorphonuclear myeloid-derived suppressor cells
We report here that colonic inflammation induces IL6 expression primarily in the CD11b+Ly6G+Ly6Clo polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in colon. Although both tumor cells, T cells and myeloid cells all express IL6, PMN-MDSCs are the primary cell type that express IL6 in colon carcinoma, suggesting that IL6 up-regulation is a response to inflammation in colon epithelium and tumor microenvironment. Furthermore, we determined that IL6 activates STAT3 to up-regulate DNMT1 and DNMT3b expression in colon tumor cells, thereby revealing an epigenetic mechanism that mediates the IL6-STAT3 signaling pathway...
Source: Cancer Immunology, Immunotherapy - June 1, 2020 Category: Cancer & Oncology Source Type: research

Seeking and destroying the evils from the inside-translating cancer immunity to fight COVID-19
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 16, 2020 Category: Cancer & Oncology Source Type: research

Successful treatment of steroid-refractory immune checkpoint inhibitor-related pneumonitis with triple combination therapy: a case report
AbstractImmune checkpoint inhibitor (ICI)-related pneumonitis is a relatively rare but clinically serious and potentially life-threatening adverse event. The majority of cases can be managed by drug discontinuation, with the administration of corticosteroids added in severe cases. However, worsening of pneumonitis can develop in a subset of patients despite treatment with high doses of corticosteroids. We herein report a case of steroid-refractory ICI-related pneumonitis in a recurrent non-small cell lung cancer (NSCLC) patient treated with pembrolizumab that was successfully improved by triple combination therapy (high-do...
Source: Cancer Immunology, Immunotherapy - May 15, 2020 Category: Cancer & Oncology Source Type: research

Prevention of liver metastases through perioperative acute CpG-C immune stimulation
AbstractFollowing excision of colorectal tumors, metastatic disease is prevalent, primarily occurs in the liver, and is highly predictive of poor prognosis. The perioperative period is now recognized as critical in determining the incidence of postoperative metastases and long-term cancer outcomes. Thus, various perioperative prophylactic interventions are currently studied during this time frame. However, immune stimulation during the perioperative period has rarely been attempted due to specific contraindications to surgery and various adverse effects. Here, to prevent liver metastases, we perioperatively employed a TLR-...
Source: Cancer Immunology, Immunotherapy - May 13, 2020 Category: Cancer & Oncology Source Type: research

The effects of tumor resection and adjuvant therapy on the peripheral blood immune cell profile in patients with colon carcinoma
ConclusionsOur results suggest tumor-induced suppression of NK- and NKT-like cells in CC patients, an effect that could not be detected after tumor resection. In contrast, adjuvant therapy maintained tumor-induced immunosuppression of NK- and NKT-like cells in CC patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 12, 2020 Category: Cancer & Oncology Source Type: research

Integrity of plasma DNA is inversely correlated with vaccine-induced antitumor immunity in ovarian cancer patients
AbstractCancer immunotherapy including vaccine therapy is a promising modality for cancer treatment, but few patients show its clinical benefits currently. The identification of biomarkers that can identify patients who will benefit from cancer immunotherapy is thus important. Here, we investigated the potential utility of the circulating cell-free DNA (cfDNA) integrity —a ratio of necrotic cell-derived, longer DNA fragments versus apoptotic cell-derived shorter fragments of Alu gene—as a biomarker of vaccine therapy for patients with ovarian cancer. We analyzed plasma samples from 39 patients with advanced or ...
Source: Cancer Immunology, Immunotherapy - May 11, 2020 Category: Cancer & Oncology Source Type: research

Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer
AbstractDespite recent advances in colorectal cancer (CRC) treatment, a large proportion of patients show limited responses to therapies, especially in advanced stages. There is an urgent need to identify prognostic biomarkers and/or therapeutic targets in advanced stages, aiming to improve the efficacy of current treatments. We aimed to determine prognostic biomarkers in tumor tissue and circulation of CRC patients, with a special focus on T cell exhaustion markers. We found that mRNA levels of PD-1, TIM-3, CTLA-4, TIGIT, CD160, CD244, KLRG1, TOX2, TOX3, Ki-67, and PRDM1 were elevated in CRC tumor tissues. We also investi...
Source: Cancer Immunology, Immunotherapy - May 11, 2020 Category: Cancer & Oncology Source Type: research

Therapeutic ISCOMATRIX ™ adjuvant vaccine elicits effective anti-tumor immunity in the TRAMP-C1 mouse model of prostate cancer
In this study, we examine the effectiveness of a therapeutic cancer vaccine that combines the ISCOMATRIX ™ adjuvant (ISCOMATRIX) with the Toll-like receptor 3 agonist, polyinosinic–polycytidylic acid (Poly I:C), and Flt3L, FMS-like tyrosine kinase 3 ligand. We employed the TRAMP-C1 (transgenic adenocarcinoma of the mouse prostate) model of prostate cancer and the self-protein mPAP (prostatic acid p hosphatase) as the tumor antigen. ISCOMATRIX™–mPAP–Poly I:C–Flt3L was delivered in a therapeutic prime-boost regime that was consistently able to achieve complete tumor regression in 60% of an...
Source: Cancer Immunology, Immunotherapy - May 9, 2020 Category: Cancer & Oncology Source Type: research

Activated HIF1 α of tumor cells promotes chemoresistance development via recruiting GDF15-producing tumor-associated macrophages in gastric cancer
AbstractChemotherapy is the preferred treatment for advanced stage gastric cancer (GC) patients, and developing chemoresistance is a tremendous challenge to efficacy of GC treatment. The treatments of anti-tumor chemo-agents recruit more tumor-associated macrophages (TAMs) which are highly implicated in the chemoresistance development, but the underlying molecular mechanism is unclear. Here, we demonstrate that hypoxia-inducible factor 1 α (HIF1α) in GC cells is activated upon 5-fluorouracil (5-FU) treatment and results in much more accumulation of M2-type TAMs which protect tumor cells from chemo-agents. Mecha...
Source: Cancer Immunology, Immunotherapy - May 9, 2020 Category: Cancer & Oncology Source Type: research

Aberrant peripheral blood CD4 + CD25 + FOXP3 + regulatory T cells/T helper-17 number is associated with the outcome of patients with lymphoma
In this study, the prognostic and clinical significance of peripheral blood Tregs and Th17 cells were evaluated in lymphoma patients during different phases. The frequency of Tregs and Th17 lymphocytes was measured by flow cytometry method in 47 classical Hodgkin ’s lymphoma (cHL) and 48 diffuse large B cell lymphoma (DLBCL) patients. Our results showed that the frequency of Tregs and absolute Treg count was significantly reduced in relapsed patients compared to patients at the remission phase, as well as with newly diagnosed untreated patients in both gro ups. Patients who reached complete remission had elevated fre...
Source: Cancer Immunology, Immunotherapy - May 8, 2020 Category: Cancer & Oncology Source Type: research

Prognostic role of PD-L1 and immune-related gene expression profiles in giant cell tumors of bone
AbstractGiant cell tumor of bone (GCTB) is a locally aggressive and rarely metastatic tumor, with a relatively unpredictable clinical course. A retrospective series of 46 GCTB and a control group of 24 aneurysmal bone cysts (ABC) were selected with the aim of investigating the PD-L1 expression levels and immune-related gene expression profile, in correlation with clinicopathological features. PD-L1 and Ki67 were immunohistochemically tested in each case. Furthermore, comprehensive molecular analyses were carried out using NanoString technology and nCounter PanCancer Immune Profiling Panel, and the gene expression results w...
Source: Cancer Immunology, Immunotherapy - May 6, 2020 Category: Cancer & Oncology Source Type: research

Interferon regulatory factor 1 (IRF-1) and IRF-2 regulate PD-L1 expression in hepatocellular carcinoma (HCC) cells
The objective response rate of immune checkpoint blockade (ICB) in hepatocellular carcinoma (HCC) with anti PD-L1/PD-1 therapy is low. Discovering the signaling pathways regulating PD-L1 might help to improve ICB response rates. Here, we investigate transcription factors IRF-1 and IRF-2 signaling pathways regulating PD-L1 in HCC cells. In vivo studies show that IRF-1 and PD-L1 mRNA expression in human HCC tumors are significantly repressed compared with noncancerous background liver. IRF-1, IRF-2, and PD-L1 mRNA expression correlated positively in HCC tumors. Increased IRF-1 mRNA expression was observed in patients with we...
Source: Cancer Immunology, Immunotherapy - May 6, 2020 Category: Cancer & Oncology Source Type: research

Cysteine cathepsins L and X differentially modulate interactions between myeloid-derived suppressor cells and tumor cells
AbstractIncreased proteolytic activity of cysteine cathepsins has long been known to facilitate malignant progression, and it has also been associated with tumor-promoting roles of myeloid-derived suppressor cells (MDSCs). Consequently, cysteine cathepsins have gained much attention as potential targets for cancer therapies. However, cross-talk between tumor cells and MDSCs needs to be taken into account when studying the efficacy of cathepsin inhibitors as anti-cancer agents. Here, we demonstrate the potential of the MDA-MB-231 breast cancer cell line to generate functional MDSCs from CD14+ cells of healthy human donors. ...
Source: Cancer Immunology, Immunotherapy - May 5, 2020 Category: Cancer & Oncology Source Type: research

A gene expression-based immune signature for lung adenocarcinoma prognosis
ConclusionsThe identified DEG features may serve as potential biomarkers for prognosis prediction of LUAD patients and immunotherapy. Based on that assumption, we identified a gene expression-based immune signature for lung adenocarcinoma prognosis. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 5, 2020 Category: Cancer & Oncology Source Type: research

CCR8 blockade primes anti-tumor immunity through intratumoral regulatory T cells destabilization in muscle-invasive bladder cancer
In this study, a retrospective analysis of 259 muscle-invasive bladder cancer (MIBC) patients from two independent clinic centers was conducted to explore the prognostic merit of CCR8+Tregs via immunohistochemistry. Eighty-three fresh MIBC samples and data from the Cancer Genome Atlas were used to evaluate the proportion and function of immune cells via flow cytometry, ex vivo intervention experiments and bioinformatics analysis. It was found that the CCR8 expression by intratumoral Tregs maintained the stability and potentiated their suppressive function by upregulating the expression of transcript factors FOXO1 and c-MAF...
Source: Cancer Immunology, Immunotherapy - May 4, 2020 Category: Cancer & Oncology Source Type: research

Comparative immunomodulatory properties of mesenchymal stem cells derived from human breast tumor and normal breast adipose tissue
ConclusionMSCs educated in stage II breast cancer and normal breast adipose tissue, although sharing a similar morphology and immunophenotype, exhibited a clearly different profile in some immunomodulatory functions and protein secretions. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 30, 2020 Category: Cancer & Oncology Source Type: research

Deep abscopal response to radiotherapy and anti-PD-1 in an oligometastatic melanoma patient with unfavorable pretreatment immune signature
We report on two elderly patients with oligometastatic melanoma treated with anti-PD-1 and stereotactic body radiation therapy (SBRT). Before treatment, patient 1 showed strong tumor infiltration with exhausted CD8+ T  cells and high expression of T cell-attracting chemokines. This patient rapidly mounted a complete response, now ongoing for more than 4.5 years. Patient 2 exhibited low CD8+ T cell infiltration and high expression of immunosuppressive arginase. After the first SBRT, his non-irradiated metasta ses did not regress and new metastases occurred although neoepitope-specific and differenti...
Source: Cancer Immunology, Immunotherapy - April 29, 2020 Category: Cancer & Oncology Source Type: research

Correction to: Outcomes associated with immune-related adverse events in metastatic non-small cell lung cancer treated with nivolumab: a pooled exploratory analysis from a global cohort
The original version of this article unfortunately contained a mistake. The second sentence of the section “irAEs and ICI efficacy” should read as. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 28, 2020 Category: Cancer & Oncology Source Type: research

Patients ’ NK cell stimulation with activated plasmacytoid dendritic cells increases dinutuximab-induced neuroblastoma killing
AbstractTargeted immunotherapy has improved the outcome of patients with high-risk neuroblastoma (NB). However, immune escape of tumor cells still occurs and about 40% of NB patients relapse and die from their disease. We previously showed that natural killer (NK) cell stimulation by Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC) increases the efficacy of dinutuximab-based immunotherapy against NB cell lines via the TRAIL death-receptor pathway. With the aim to translate our findings into a novel adoptive therapy of TLR-activated pDC, we investigated the pDC/NK cell axis in NB patients undergoing din...
Source: Cancer Immunology, Immunotherapy - April 27, 2020 Category: Cancer & Oncology Source Type: research

In-depth characterization of the tumor microenvironment in central nervous system lymphoma reveals implications for immune-checkpoint therapy
In conclusion, the clinical impact of TME composition supports the use of immune-checkpoint therapies in PCNSL. Based on observed differences in immune-checkpoint expression, combinations that boost cytotoxic T cell activation (by blocking TIM-3 or TGFBR1) prior to the administration of PD-L1 inhibition could be of interest. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 25, 2020 Category: Cancer & Oncology Source Type: research

Peri-tumor administration of controlled release anti-CTLA-4 synergizes with systemic anti-PD-1 to induce systemic antitumor immunity while sparing autoimmune toxicity
AbstractCombination immunotherapy targeting the PD-1 and CTLA-4 checkpoint inhibitor pathways provides substantial clinical benefit in patients with advanced-stage cancer but at the risk of dose-limiting inflammatory and autoimmune toxicity. The delicate balance that exists between unleashing tumor killing and promoting systemic autoimmune toxicity represents a major clinical challenge. We hypothesized that targeting anti-CTLA-4 so that it perfuses tumor-draining lymph nodes would provide a significant therapeutic advantage and developed an injectable hydrogel with controlled antibody release characteristics for this purpo...
Source: Cancer Immunology, Immunotherapy - April 24, 2020 Category: Cancer & Oncology Source Type: research

Combining doxorubicin with stearylamine-bearing liposomes elicits Th1 cytokine responses and cures metastasis in a mouse model
AbstractSurface exposed phosphatidylserine (PS) of cancer aids it to evade immune surveillance and thereby results in tumor progression. Earlier, we reported that PS targeting cationic liposomes, phosphatidylcholine –stearylamine (PC-SA), alone and in combination with doxorubicin can result in complete remission of B16F10 melanoma in C57BL/6 mice without signs of toxicity. Inducing an immunogenic response is highly crucial for any cancer therapy as it is essential in improving the tumor microenvironment for any drug to act. Herein, we demonstrate that PC-SA, besides having tumor reducing ability, elicits a stron...
Source: Cancer Immunology, Immunotherapy - April 24, 2020 Category: Cancer & Oncology Source Type: research

Cryoablation combined with transarterial infusion of pembrolizumab (CATAP) for liver metastases of melanoma: an ambispective, proof-of-concept cohort study
ConclusionsThe CATAP therapy demonstrated positive clinical activity and a favorable  safety profile for melanoma patients with liver metastasis. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 24, 2020 Category: Cancer & Oncology Source Type: research

IL-12 regulates the expansion, phenotype, and function of murine NK cells activated by IL-15 and IL-18
AbstractNK cells, which are composed of phenotypically and functionally heterogeneous subpopulations, play critical roles in immunity against cancer. The mechanism of generation of distinct subsets such as the effector and regulatory subtypes is unclear. Here, we show that this process comprises several steps, including generation of proliferating, highly cytotoxic cells activated by IL-15/IL-18 and differentiation into distinct cell populations induced with IL-12. Freshly prepared murine splenic NK cells expressed IL-15Rs and IL-18Rs and rapidly began to proliferate following stimulation with IL-15/IL-18. The proliferatin...
Source: Cancer Immunology, Immunotherapy - April 24, 2020 Category: Cancer & Oncology Source Type: research

Advances and perspectives of dendritic cell-based active immunotherapies in follicular lymphoma
AbstractFollicular lymphoma (FL) is a remarkably immune-responsive malignancy, which is still considered incurable. As, standard immunochemotherapy is complex, toxic and not curative, improvement in FL care is now a crucial topic in hemato-oncology. Recently, we and others have shown that dendritic cell (DC)-based therapies allow a specific immune response associated with sustained lymphoma regression in a proportion of low-tumor burden FL patients. Importantly, the rate of objective clinical response (33 –50%) and of sustained remission is remarkably higher compared to similar studies in solid tumors, corroborating ...
Source: Cancer Immunology, Immunotherapy - April 22, 2020 Category: Cancer & Oncology Source Type: research

NK1R antagonist decreases inflammation and metastasis of breast carcinoma cells metastasized to liver but not to brain; phenotype-dependent therapeutic and toxic consequences
AbstractSubstance P a neuro-immune mediator acts on Neurokinin-1 and -2 receptors (NK1R and NK2R). Inhibitors of NK1R are considered to be safe and effective approaches for cancer treatment since Aprepitant, a non-peptide antagonist of NK1R is widely used for chemotherapy-induced emesis and has cytotoxic and antitumor effects in various models for cancer. On the other hand, our previous findings demonstrated that systemic inhibition of NK1R may decrease cytotoxic anti-tumoral immune response. Hence, actual consequences of inhibition of neurokinin receptors under in vivo conditions in a syngeneic model of carcinoma should b...
Source: Cancer Immunology, Immunotherapy - April 22, 2020 Category: Cancer & Oncology Source Type: research

Prevalence of PD-L1 expression is associated with EMAST, density of peritumoral T-cells and recurrence-free survival in operable non-metastatic colorectal cancer
ConclusionsHigher Immunoscore (CD3/CD8 cells) and expression of tumour PD-L1 is found in CRCs with EMAST. Lymphocytic infiltrate and peritumoral PD-L1 expression have prognostic value in CRC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 20, 2020 Category: Cancer & Oncology Source Type: research

Epstein –Barr virus (EBV) and polyomaviruses are detectable in oropharyngeal cancer and EBV may have prognostic impact
ConclusionPolyomaviruses are detectable in OPSCC but seem to have no impact on survival, whereas HPV was the strongest viral prognostic factor. EBER expression, as a sign of latent EBV infection, may have prognostic impact among patients with HPV-negative OPSCC. EBER analysis may identify a new subgroup of OPSCCs unrelated to HPV. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 20, 2020 Category: Cancer & Oncology Source Type: research

Energy metabolism and cell motility defect in NK-cells from patients with hepatocellular carcinoma
AbstractFunctional rescue of NK-cells in solid tumors represents a central aim for new immunotherapeutic strategies. We have conducted a genomic, phenotypic and functional analysis of circulating NK-cells from patients with HCV-related liver cirrhosis and hepatocellular carcinoma. NK-cells were sorted from patients with HCC or liver cirrhosis and from healthy donors. Comparative mRNA gene expression profiling by whole-human-genome microarrays of sorted NK-cells was followed by phenotypic and functional characterization. To further identify possible mediators of NK-cell dysfunction, an in vitro model using media conditioned...
Source: Cancer Immunology, Immunotherapy - April 19, 2020 Category: Cancer & Oncology Source Type: research

Outcomes with immune checkpoint inhibitors for relapsed small-cell lung cancer in a Swiss cohort
ConclusionThis is the first report of “real-world” data on ICI in relapsed SCLC also including patients with poor PS. Promising durable responses were observed. No biological prognostic marker could be identified. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 19, 2020 Category: Cancer & Oncology Source Type: research

Characterising the prognostic potential of HLA-DR during colorectal cancer development
AbstractHLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma –adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as ...
Source: Cancer Immunology, Immunotherapy - April 18, 2020 Category: Cancer & Oncology Source Type: research

Tumor infiltrating lymphocytes as adjuvant treatment in stage III melanoma patients with only one invaded lymph node after complete resection: results from a multicentre, randomized clinical phase III trial
ConclusionWe did not confirm results of a previous trial. However, ulceration of the primary melanoma may be considered predictive of the efficacy of TIL in melanoma in adjuvant setting, in a manner similar to interferon α. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 18, 2020 Category: Cancer & Oncology Source Type: research

Prognostic impact of stromal and intratumoral CD3, CD8 and FOXP3 in adjuvantly treated breast cancer: do they add information over stromal tumor-infiltrating lymphocyte density?
We examined 1011 patients (median follow-up 130.9  months) and their tumors for total, stromal (s) and intratumoral (i) CD3, CD8 and FOXP3 lymphocyte density (counts/mm2) on tissue-microarray cores by immunohistochemistry. Morphological sTIL density on whole H&E-stained sections was also evaluated.ResultsThe majority of TILs were CD3+. Total CD3 and CD8, sCD3 and sCD8, iCD3 and iCD8, sFOXP3 and iFOXP3 were strongly correlated (Spearman ’s rho values >  0.6). High individual lymphocytic subsets and sTIL density were strongly associated with high tumor grade, higher proliferation and HER2-posi...
Source: Cancer Immunology, Immunotherapy - April 18, 2020 Category: Cancer & Oncology Source Type: research

Tumor-infiltrating CD39 + CD8 + T cells determine poor prognosis and immune evasion in clear cell renal cell carcinoma patients
AbstractPurposeTumor microenvironment is important in the progression of clear cell renal cell carcinoma (ccRCC), and its prognostic value is still unclear. Recent reports demonstrated tumor-infiltrating CD39+CD8+ T cells are abundant, but their function remains obscure. We aim to assess clinical value of CD39+CD8+ T cells and seek a potential therapeutic target in ccRCC.Experimental designWe immunohistochemically evaluated clinical value of CD39+CD8+ T cells in a retrospective Zhongshan Hospital cohort of 243 ccRCC patients. Fresh tumor samples (n = 48), non-tumor tissues and peripheral blood for flow cytome...
Source: Cancer Immunology, Immunotherapy - April 18, 2020 Category: Cancer & Oncology Source Type: research

18 F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer
In this study, we characterized the relationships among tumor18F-fluorodeoxyglucose (FDG) retention, tumor metabolic and immune phenotypes, and survival in patients with resected non-small cell lung cancer (NSCLC). We retrospectively analyzed tumor preoperative positron emission tomography (PET)18F-FDG uptake in 59 resected NSCLCs and investigated correlations between PET parameters (SUVMax, SUVTotal, SUVMean, TLG), tumor expression of glycolysis- and immune-related genes, and tumor-associated immune cell densities that were quantified by immunohistochemistry. Tumor glycolysis-associated immune gene signatures were analyze...
Source: Cancer Immunology, Immunotherapy - April 16, 2020 Category: Cancer & Oncology Source Type: research

Characterization of an HLA-restricted and human cytomegalovirus-specific antibody repertoire with therapeutic potential
AbstractWith an infection rate of 60 –90%, the human cytomegalovirus (HCMV) is very common among adults but normally causes no symptoms. When T cell-mediated immunity is compromised, HCMV reactivation can lead to increased morbidity and mortality. HCMV antigens are processed and presented as peptides on the cell surface via HLA I com plexes to the T cell receptor (TCR) of T cells. The generation of antibodies against HCMV peptides presented on HLA complexes (TCR-like antibodies) has been described, but is without therapeutic applications to date due to the polygenic and polymorphic nature of HLA genes. We set out to ...
Source: Cancer Immunology, Immunotherapy - April 16, 2020 Category: Cancer & Oncology Source Type: research

PD-1 + natural killer cells in human non-small cell lung cancer can be activated by PD-1/PD-L1 blockade
In this study, we show that intratumoral NK cells from NSCLC patients expressed elevated levels of the immune checkpoint receptor PD-1 on their cell surface. In contrast to the expression of activating receptors, PD-1+ NK cells co-expressed more inhibitory receptors compared to PD-1− NK cells. Intratumoral NK cells were less functional compared to peripheral NK cells, and this dysfunction correlated with PD-1 expression. Tumor cells expressing PD-L1 inhibited the functionality of PD-1+ NK cells in ex vivo models and induced PD-1 clustering at the immunological synapse between NK cells and tumor cells. Notably, treatm...
Source: Cancer Immunology, Immunotherapy - April 15, 2020 Category: Cancer & Oncology Source Type: research

Combined blockade of TGf- β1 and GM-CSF improves chemotherapeutic effects for pancreatic cancer by modulating tumor microenvironment
This study presents a novel promising combined strategy to improve the chemotherapeutic effects for pancreatic cancer. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 13, 2020 Category: Cancer & Oncology Source Type: research

Interleukin-33 pretreatment promotes metastatic growth of murine melanoma by reducing the cytotoxic capacity of CD8 + T cells and enhancing regulatory T cells
AbstractInterleukin-33 (IL-33) regulates innate and acquired immune response to pathogens, self-antigens and tumors. IL-33 effects on tumors depend on the dose and mode of administration along with the type of malignancy. We studied the effects of IL-33 on the development of primary and metastatic melanoma induced by B16-F1 cell line in C57BL/6 mice. Intraperitoneally applied IL-33 restricts primary tumor growth. When administered intranasally 3  days prior to the intravenous injection of the tumor cells, IL-33 promoted growth of B16-F1 melanoma metastases, while B16-F10 gave massive metastases independently of IL-33....
Source: Cancer Immunology, Immunotherapy - April 13, 2020 Category: Cancer & Oncology Source Type: research

Characterization of CD103 + CD8 + tissue-resident T cells in esophageal squamous cell carcinoma: may be tumor reactive and resurrected by anti-PD-1 blockade
This study emphasized the feature of CD103+ CD8+ TILs in immune response and identified potentially new targets in ESCC patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 13, 2020 Category: Cancer & Oncology Source Type: research

Neuroendocrine tumours and their microenvironment
AbstractTumours can escape the immune system by expressing programmed death-ligand-1 (PD-L1), which allows them to bind to PD-1 on T-cells and avoid recognition by the immune system. Regulatory T-cells (Tregs), indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) also play a role in immune suppression. Knowledge about the interaction of neuroendocrine tumours (NETs) with their immune microenvironment and the role of immunotherapy in patients with NET is scarce. Here, we investigated the immune microenvironment of serotonin-producing (SP) and non-serotonin-producing NETs (NSP-NETs). Tumours of 33 patients ...
Source: Cancer Immunology, Immunotherapy - April 8, 2020 Category: Cancer & Oncology Source Type: research

Expression of the immune checkpoint VISTA in breast cancer
This study aimed to investigate the expression of VISTA and its association with clinicopathologic parameters as weNll as with the key immune markers including programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) in invasive ductal carcinoma (IDC) of the breast. Immunohistochemistry was used to detect VISTA, PD-1, PD-L1, and CD8 in tissue microarrays from 919 patients with IDC (N = 341 in the exploratory cohort and  = 578 in the validation cohort). VISTA was expressed on the immune cells of 29.1% (267/919) of the samples and on the tumor cells of 8.2% (75/919). VISTA was more frequently expr...
Source: Cancer Immunology, Immunotherapy - April 7, 2020 Category: Cancer & Oncology Source Type: research

The glucocorticoids prednisone and dexamethasone differentially modulate T cell function in response to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade
AbstractOn-treatment steroids for countering immune checkpoint inhibitor-induced inflammatory responses (irAEs) are a hallmark of cancer immunotherapy. However, the suppressive nature of steroids has raised questions regarding their ability to compromise the function of the ‘proliferative burst’ of effector T cells induced by immune checkpoint antibodies. We investigated the effector functions and the co-inhibitory receptor profile of stimulated peripheral blood mononuclear cells (PBMCs) pre-treated with prednisone and dexamethasone alone or in the presence of anti -PD-1/CTLA-4 antibodies. Also, clinical analys...
Source: Cancer Immunology, Immunotherapy - April 3, 2020 Category: Cancer & Oncology Source Type: research

Knocking out matrix metalloproteinase 12 causes the accumulation of M2 macrophages in intestinal tumor microenvironment of mice
AbstractMMP12 is mainly secreted by macrophages, is involved in macrophage development, and decomposes the extracellular matrix. Herein, we investigated whether macrophages would change in the intestinal tumor microenvironment after MMP12 knockout. ApcMin/+;MMP12−/−mice were obtained by crossbreeding ApcMin/+ mice with MMP12 knockout mice (MMP12−/− mice). The data showed that the number and volume of intestinal tumors were significantly increased in ApcMin/+;MMP12−/− mice compared with ApcMin/+ mice. Additionally, the tumor biomarkers CA19-9, CEA, and β-catenin appeared relatively e...
Source: Cancer Immunology, Immunotherapy - April 2, 2020 Category: Cancer & Oncology Source Type: research

Lymphocyte activation gene 3 (LAG3) protein expression on tumor-infiltrating lymphocytes in aggressive and TP53 -mutated salivary gland carcinomas
AbstractSalivary gland carcinomas (SGCs) are rare and can be subdivided into distinct entities, some of which confer a poor prognosis. As targets for effective systemic therapy are warranted, some studies investigated the role of immune-checkpoint proteins PD-L1 and CTLA-4 in SGC. Our study depicts the expression of lymphocyte activation gene 3(LAG3) in a test cohort and a larger validation cohort, totaling 139 SGCs. LAG3 is expressed on tumor-infiltrating lymphocytes (TILs), mediates T cell exhaustion and is subject to numerous currently recruiting clinical studies. Overall, one-third of SGCs were infiltrated by LAG3-expr...
Source: Cancer Immunology, Immunotherapy - March 30, 2020 Category: Cancer & Oncology Source Type: research

A comparative view on the expression patterns of PD-L1 and PD-1 in soft tissue sarcomas
AbstractSoft tissue sarcomas (STSs) are heterogeneous cancers associated with poor prognosis due to high rates of local recurrence and metastasis. The programmed death receptor ligand 1 (PD-L1) is expressed in several cancers. PD-L1 interacts with its receptor, PD-1, on the surface of tumor-infiltrating lymphocytes (TILs), thereby attenuating anti-cancer immune response. Immune checkpoint inhibitors targeting this interaction have been established as effective anti-cancer drugs. However, studies on the PD-L1 and PD-1 expression status in STS are commonly limited by small sample size, analysis of single STS subtypes, or lac...
Source: Cancer Immunology, Immunotherapy - March 28, 2020 Category: Cancer & Oncology Source Type: research

In vivo anti-MUC1 + tumor activity and sequences of high-affinity anti-MUC1-SEA antibodies
AbstractCleavage of the MUC1 glycoprotein yields two subunits, an extracellular alpha-subunit bound to a smaller transmembrane beta-subunit. Monoclonal antibodies (mAbs) directed against the MUC1 alpha –beta junction comprising the SEA domain, a stable cell-surface moiety, were generated. Sequencing of all seven anti-SEA domain mAbs showed that they clustered into four groups and sequences of all groups are presented here. mAb DMB5F3 with picomolar affinity for the MUC1 SEA target was selected f or further evaluation. Immunohistochemical staining of a series of malignancies with DMB5F3 including lung, prostate, breas...
Source: Cancer Immunology, Immunotherapy - March 26, 2020 Category: Cancer & Oncology Source Type: research

A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial
ConclusionsThis novel peptide vaccination therapy was safe for patients with metastatic gastrointestinal cancers. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 26, 2020 Category: Cancer & Oncology Source Type: research

Correction to: Translational immune correlates of indirect antibody immunization in a randomized phase II study using scheduled combination therapy with carboplatin/paclitaxel plus oregovomab in ovarian cancer patients
The original version of this article unfortunately contained a mistake. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 26, 2020 Category: Cancer & Oncology Source Type: research

Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade
In this study, we have established and optimised an in vitro tumour-immune co-culture system (TICS), which is specifically designed to quantify the activation of multiple primary human lymphocyte subsets and human cancer cell killing in response to PD-1/L1 blockade. Human OC cell lines and treatment na ïve patient ascites show differential effects on lymphocyte activation and respond differently to PD-1 blocking antibody nivolumab in TICS. Using paired OC cell lines established prior to and after chemotherapy relapse, our data reveal that the resistant cells express low levels of HLA and respond poorly to nivolumab, r...
Source: Cancer Immunology, Immunotherapy - March 21, 2020 Category: Cancer & Oncology Source Type: research