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

Lauren classification identifies distinct prognostic value and functional status of intratumoral CD8 + T cells in gastric cancer
This study was aimed to evaluate the functional impact of Lauren classification on immune contexture in gastric cancer patients. Tumor tissues of gastric cancer patients from Zhongshan Hospital and gastric cancer data from The Cancer Genome Atlas (TCGA) cohort were analyzed. By immunohistochemistry and flow cytometry, we found that intratumoral CD8+ T cells were more abundant but less functional in diffuse type as compared with those in intestinal type tumor tissues. Survival analysis indicated that CD8+ T cells yielded favorable prognosis only in intestinal type patients other than diffuse type cancer patients. Moreover, ...
Source: Cancer Immunology, Immunotherapy - March 21, 2020 Category: Cancer & Oncology Source Type: research

TNFR2+ TILs are significantly associated with improved survival in triple-negative breast cancer patients
AbstractIn view of the relatively limited efficacy of immunotherapies targeting the PD-1 –PD-L1 axis in triple-negative breast cancer (TNBC) and of published reports on tumor-promoting roles of TNFR2+ tumor-infiltrating lymphocytes (TNFR2+ TILs), we determined the incidence of TNFR2+ TILs in TNBC patient tumors, their association with disease outcome and relations with PD-1+ TILs. Usi ng a cohort of treatment-naïve TNBC patients with long follow-up (n = 70), we determined the presence of TNFR2+ TILs and PD-1+ TILs by immunohistochemistry. TILs (≥ 1% of cellular mass) and TNFR2+ TILs (≥...
Source: Cancer Immunology, Immunotherapy - March 20, 2020 Category: Cancer & Oncology Source Type: research

Upregulated immuno-modulator PD-L1 in malignant peripheral nerve sheath tumors provides a potential biomarker and a therapeutic target
ConclusionThe immuno-modulator PD-L1 is upregulated in MPNST patients and therefore may provide as a potential biomarker of malignant transformation in patients with NF1 and as a response predictor for immunotherapeutic approaches. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 19, 2020 Category: Cancer & Oncology Source Type: research

Identification and validation of tumor environment phenotypes in lung adenocarcinoma by integrative genome-scale analysis
ConclusionsOur findings describe a comprehensive landscape of LUAD immune infiltration pattern and integrate several previously proposed biomarkers associated with distinct immunophenotypes, thus shedding light on how tumors interact with immune microenvironment. Our results may guide a more precise immune therapeutic strategy for LUAD patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 18, 2020 Category: Cancer & Oncology Source Type: research

Regulatory T cells specifically suppress conventional CD8 αβ T cells in intestinal tumors of APC Min/+ mice
In this study, we investigated the effect of Treg depletion on the density and effector functions of different TCR αβ+ and TCR γδ+ T cell populations in intestinal tumors. We used the APCMin/+\DEREG mouse model, which harbor a diphtheria toxin receptor under the control of the FOXP3 promoter, to deplete Treg in tumor bearing mice. We found that the density of conventional TCR αβ+CD8 αβ+ T cells was significantly increased in Treg-depleted tumors in comparison with Treg-proficient tumors. Furthermore, TCR αβ+CD8 αβ+ T cells showed increased proliferation and...
Source: Cancer Immunology, Immunotherapy - March 17, 2020 Category: Cancer & Oncology Source Type: research

Differential expression of Tim-3, PD-1, and CCR5 on peripheral T and B lymphocytes in hepatitis C virus-related hepatocellular carcinoma and their impact on treatment outcomes
ConclusionModulation of the expression of immune checkpoints as Tim-3 and PD-1, and of CCR5 on T cells is somehow related to HCC. CD8+ T cells expressing PD-1 were the most relevant to HCC prognosis (OS and treatment response) and could represent a promising target for immune therapy against HCC. Future studies need to focus on exploring PD-1+ B cells and Tim-3+CD4+ cells, which seem to play a significant role in the pathogenesis of HCC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 13, 2020 Category: Cancer & Oncology Source Type: research

Tumor immune microenvironment in cancer patients with leukocytosis
AbstractTumor-related leukocytosis (TRL) is correlated with poor survival in various types of cancers, but the microenvironment of TRL-associated human tumors has not been fully elucidated. Here, we aimed to characterize the immune microenvironment of cancer patients with TRL. The transcriptional signatures of tumor tissues obtained from cervical cancer patients with (TRLpos) and without TRL (TRLneg) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRLpos and TRLneg tumors. The immunological profiles of patients in the TCGA databas...
Source: Cancer Immunology, Immunotherapy - March 13, 2020 Category: Cancer & Oncology Source Type: research

Comprehensive landscape of immune-checkpoints uncovered in clear cell renal cell carcinoma reveals new and emerging therapeutic targets
AbstractClear cell renal cell carcinoma (ccRCC) constitutes the most common renal cell carcinoma subtype and has long been recognized as an immunogenic cancer. As such, significant attention has been directed toward optimizing immune-checkpoints (IC)-based therapies. Despite proven benefits, a substantial number of patients remain unresponsive to treatment, suggesting that yet unreported, immunosuppressive mechanisms coexist within tumors and their microenvironment. Here, we comprehensively analyzed and ranked forty-four immune-checkpoints expressed in ccRCC on the basis of in ‐depth analysis of RNAseq data collected fro...
Source: Cancer Immunology, Immunotherapy - March 12, 2020 Category: Cancer & Oncology Source Type: research

Correction to: Predictive value of positron emission tomography for the prognosis of immune checkpoint inhibitors (ICIs) in malignant tumors
The original version of this article unfortunately contained a mistake. The correct information is given in the following. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 11, 2020 Category: Cancer & Oncology Source Type: research

Cancer testis antigen Cyclin A1 harbors several HLA-A*02:01-restricted T cell epitopes, which are presented and recognized in vivo
AbstractCyclin A1 is a promising antigen for T cell therapy being selectively expressed in high-grade ovarian cancer (OC) and acute myeloid leukemia (AML) stem cells. For adoptive T cell therapy, a single epitope has to be selected, with high affinity to MHC class I and adequate processing and presentation by malignant cells to trigger full activation of specific T cells. In silico prediction with three algorithms indicated 13 peptides of Cyclin A1 9 to 11 amino acids of length to have high affinity to HLA-A*02:01. Ten of them proved to be affine in an HLA stabilization assay using TAP-deficient T2 cells. Their immunogenic...
Source: Cancer Immunology, Immunotherapy - March 10, 2020 Category: Cancer & Oncology Source Type: research

Predictive value of serum VEGF levels for elderly patients or for patients with poor performance status receiving anti-PD-1 antibody therapy for advanced non-small-cell lung cancer
This study aimed to find a predictive biomarker for the efficacy of anti-programmed cell death 1 (PD-1) antibodies in these patient populations. We retrospectively reviewed medical records of advanced non-small-cell lung cancer (NSCLC) patients who were  ≥ 75 years of age or classified as PS 2 and received anti-PD-1 antibody treatment between December 2015 and May 2018. We evaluated the association between the efficacy of the anti-PD-1 antibody in these patients and the clinical variables thought to affect ICI efficacy. A total of 235 patien ts with advanced NSCLC were treated with anti-PD-1 antibodie...
Source: Cancer Immunology, Immunotherapy - March 10, 2020 Category: Cancer & Oncology Source Type: research

Significant association between tumor mutational burden and immune-related adverse events during immune checkpoint inhibition therapies
AbstractMore than 2000 immuno-oncology agents are being tested or are in use as a result of the cancer immunotherapy revolution. Manipulation of co-inhibitory receptors has achieved tumor eradication in a minority of patients, but widespread immune-related adverse events (irAEs) compromised tolerance to healthy self-tissues in the majority. We have proposed that a major mechanism of irAEs is similar to a graft-versus-malignancy effect of graft-versus-host disease. To verify our hypothesis, we retrieved post-marketing data of adverse events from the U.S. Food and Drug Administration Adverse Event Reporting System. A signifi...
Source: Cancer Immunology, Immunotherapy - March 9, 2020 Category: Cancer & Oncology Source Type: research

ESTIMATE algorithm is not appropriate for inferring tumor purity and stromal and immune cell admixture in hematopoietic or stromal tumors
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 9, 2020 Category: Cancer & Oncology Source Type: research

Adenosine-producing regulatory B cells in head and neck cancer
ConclusionOur data demonstrate the presence of a novel ADO-producing Breg population within the tumor microenvironment in mice and humans. A new model is proposed on how ADO-producing Breg can influence the function of Beff cells in healthy donors and cancer patients. Thus, the modulation of the ADO pathway in B cells may serve as a therapeutic approach for cancer patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 7, 2020 Category: Cancer & Oncology Source Type: research

Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy
In this study, we evaluated whether TTFields-mediated cell death can elicit antitumoral immunity and hence would be effectively combined with anti-PD-1 therapy. We demonstrate that in TTFields-treated cancer cells, damage-associated molecular patterns including high-mobility group B1 and adenosine triphosphate are released and calreticulin is exposed on the cell surface. Moreover, we show that TTFields treatment promotes the engulfment of cancer cells by dendritic cells (DCs) and DCs maturation in vitro, as well as recruitment of immune cells in vivo. Additionally, our study demonstrates that the combination of TTFields wi...
Source: Cancer Immunology, Immunotherapy - March 6, 2020 Category: Cancer & Oncology Source Type: research

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
AbstractBackgroundImmune-related adverse events (irAEs) comprise a distinct spectrum of auto-inflammatory manifestations triggered due to immune checkpoint inhibitors (ICI). Current data on the association of irAEs with outcomes in NSCLC treated with nivolumab are limited.Methods and objectivesWe pooled data from 531 metastatic NSCLC patients from five centers treated with nivolumab after failing platinum-based chemotherapy.  The primary objective was to investigate the relationship between irAEs with clinical benefit to nivolumab as well as to elucidate patterns of irAE-related ICI discontinuations and their impact o...
Source: Cancer Immunology, Immunotherapy - March 5, 2020 Category: Cancer & Oncology Source Type: research

Less is more: reducing the number of administered chimeric antigen receptor T cells in a mouse model using a mathematically guided approach
AbstractChimeric antigen receptor T cell (CAR-T) therapy is a novel approved treatment for hematological malignancies, still under development for solid tumors. Here, we use a rate equation-based mathematical model to discover regimens and schedules that maintain efficacy while potentially reducing toxicity by decreasing the amount of CAR-T infused. Tested on an in vivo murine model of spontaneous breast cancer, we show that our mathematical model accurately recapitulates in vivo tumor growth results achieved in the previous experiments. Moreover, we use the mathematical model to predict results of new therapy schedules an...
Source: Cancer Immunology, Immunotherapy - March 4, 2020 Category: Cancer & Oncology Source Type: research

Current progress in NK cell biology and NK cell-based cancer immunotherapy
AbstractA better understanding of the complex interactions between the immune system and tumour cells from different origins has opened the possibility to design novel procedures of antitumoral immunotherapy. One of these novel approaches is based on the use of autologous or allogeneic natural killer (NK) cells to treat cancer. In the last decade, different strategies to activate NK cells and their use in adoptive NK cell-based therapy have been established. Although NK cells are often considered as a uniform cell population, several phenotypic and functionally distinct NK cells subsets exist in healthy individuals, that a...
Source: Cancer Immunology, Immunotherapy - March 4, 2020 Category: Cancer & Oncology Source Type: research

International Regensburg Center for Interventional Immunology (RCI) symposium on “Synthetic immunology and environment-adapted redirection of T cells”, 17–18 July, 2019, Regensburg, Germany
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 2, 2020 Category: Cancer & Oncology Source Type: research

Genome-wide association study of genetic variations associated with treatment failure after intravesical bacillus Calmette –Guérin therapy for non-muscle invasive bladder cancer
This study included 91 Japanese patients treated with BCG instillation for NMIBC. Genomic DNA was obtained from patient whole-blood samples, and a genome-wide association study and genotyping for target regions were performed. The association between genetic vari ation and treatment failure was analyzed by genome-wide association in 44 patients as the discovery cohort. As a validation study, candidate single nucleotide polymorphisms (SNPs) were examined among 47 patients in another cohort. The genome-wide association study indicated 19 candidate SNPs (rs1607 282, rs7825442, rs1319325, rs3738088, rs4250, rs11894207, rs16144...
Source: Cancer Immunology, Immunotherapy - March 2, 2020 Category: Cancer & Oncology Source Type: research

Neutrophils are mediators of metastatic prostate cancer progression in bone
AbstractBone metastatic prostate cancer (BM-PCa) significantly reduces overall patient survival and is currently incurable. Current standard immunotherapy showed promising results for PCa patients with metastatic, but less advanced, disease (i.e., fewer than 20 bone lesions) suggesting that PCa growth in bone contributes to response to immunotherapy. We found that: (1) PCa stimulates recruitment of neutrophils, the most abundant immune cell in bone, and (2) that neutrophils heavily infiltrate regions of prostate tumor in bone of BM-PCa patients. Based on these findings, we examined the impact of direct neutrophil –pr...
Source: Cancer Immunology, Immunotherapy - February 29, 2020 Category: Cancer & Oncology Source Type: research

Inhibition of IDO leads to IL-6-dependent systemic inflammation in mice when combined with photodynamic therapy
AbstractIt was previously reported that the activation of antitumor immune response by photodynamic therapy (PDT) is crucial for its therapeutic outcome. Excessive PDT-mediated inflammation is accompanied by immunosuppressive mechanisms that protect tissues from destruction. Thus, the final effect of PDT strongly depends on the balance between the activation of an adoptive arm of immune response and a range of activated immunosuppressive mechanisms. Here, with flow cytometry and functional tests, we evaluate the immunosuppressive activity of tumor-associated myeloid cells after PDT. We investigate the antitumor potential o...
Source: Cancer Immunology, Immunotherapy - February 28, 2020 Category: Cancer & Oncology Source Type: research

Clinical relevance of the comparative expression of immune checkpoint markers with the clinicopathological findings in patients with primary and chemoreduced retinoblastoma
ConclusionsThis is the first of its kind study predicting a relevant role of the immune checkpoint markers in both groups of primary and chemoreduced retinoblastoma with prognostic significance. Differential expression of these markers in both group of retinoblastoma is a novel finding and might be an interesting and beneficial target for chemoresistant tumors. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 26, 2020 Category: Cancer & Oncology Source Type: research

Myeloid-derived suppressor cells impede T cell functionality and promote Th17 differentiation in oral squamous cell carcinoma
AbstractOral tumor microenvironment is characterized by chronic inflammation signified with infiltrating leukocytes and soluble mediators which cause immune suppression. However, how immunosuppressive cells like myeloid-derived suppressor cells (MDSCs) maintain the immunosuppressive tumor microenvironment and influence T cell function in oral squamous cell carcinoma (OSCC) patients remains poorly understood. In the present study, we found that percentages of MDSCs were higher in oral cancer patients compared to healthy individuals and correlated with cancer stage. Monocytic MDSCs (M-MDSCs) were prevalent in the periphery, ...
Source: Cancer Immunology, Immunotherapy - February 26, 2020 Category: Cancer & Oncology Source Type: research

Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival
ConclusionEAC shows an anti-inflammatory environment, which strongly affects patient survival. The microscopically unaltered peritumoral tissue shows a similar anti-inflammatory pattern indicating an immunological field effect, which might contribute to early local recurrences despite radical resection. These data suggest that using checkpoint inhibitors targeting anti-inflammatory T cells would be a promising therapeutic strategy in EAC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 25, 2020 Category: Cancer & Oncology Source Type: research

Identification and validation of tumour microenvironment-based immune molecular subgroups for gastric cancer: immunotherapeutic implications
AbstractBackgroundImmunotherapy could trigger durable response in advanced gastric cancer, but it only benefits a minority of patients. We aimed to propose a robust molecular classification of gastric cancer microenvironment to identify ideal candidates for tailoring effective immunotherapy.MethodsA training cohort of 375 gastric cancer samples with RNA sequencing data was analysed. We virtually microdissected tumour, stromal, and immune cell gene expression patterns employing a non-negative matrix factorization algorithm. These expression patterns were annotated using immune- and stromal-related gene signatures. Validatio...
Source: Cancer Immunology, Immunotherapy - February 25, 2020 Category: Cancer & Oncology Source Type: research

Prostaglandin E 2 in a TLR3- and 7/8-agonist-based DC maturation cocktail generates mature, cytokine-producing, migratory DCs but impairs antigen cross-presentation to CD8 + T cells
In conclusion, TLR-P matured DCs might be optimal presenters of antigens not requiring processing such as short peptides. However, PGE2 seems less favorable for maturation of DCs intended to process and cross-present more complex vaccine antigens such as lysates, proteins or long peptides. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 25, 2020 Category: Cancer & Oncology Source Type: research

Oncolytic Newcastle disease virus activation of the innate immune response and priming of antitumor adaptive responses in vitro
AbstractOncolytic virus (OV) therapy is an emerging approach with the potential to redefine treatment options across a range of cancer indications and in patients who remain resistant to existing standards of care, including immuno-oncology (IO) drugs. MEDI5395, a recombinant Newcastle disease virus (NDV), engineered to express granulocyte –macrophage colony-stimulating factor (GM-CSF), exhibits potent oncolytic activity. It was hypothesized that activation of immune cells by MEDI5395, coupled with its oncolytic activity, would enhance the priming of antitumor immunity. Using MEDI5395 and recombinant NDVs encoding fl...
Source: Cancer Immunology, Immunotherapy - February 22, 2020 Category: Cancer & Oncology Source Type: research

Critical role of PD-L1 expression on non-tumor cells rather than on tumor cells for effective anti-PD-L1 immunotherapy in a transplantable mouse hematopoietic tumor model
AbstractThe expression of PD-L1 on tumor cells or within the tumor microenvironment has been associated with good prognosis and sustained clinical responses in immunotherapeutic regimens based on PD-L1/PD-1/CD80 immune checkpoint blockade. To look into the current controversy in cancer immunotherapy of the relative importance of PD-L1 expression on tumor cells versus non-tumor cells of the tumor microenvironment, a hematological mouse tumor model was chosen. By combining a genetic CRISPR/Cas9 and immunotherapeutic approach and using a syngeneic hematopoietic transplantable tumor model (E.G7-cOVA tumor cells), we demonstrat...
Source: Cancer Immunology, Immunotherapy - February 22, 2020 Category: Cancer & Oncology Source Type: research

Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer
AbstractColorectal cancer (CRC) patients with metastatic lesions have low 5-year survival rates. During metastasis, cancer cells often obtain unique characteristics such as epithelial –mesenchymal transition (EMT). Vimentin a biomarker contributes to EMT by changing cell shape and motility. Since abnormal phosphorylation is a hallmark of malignancy, targeting phosphorylated vimentin is a feasible approach for the treatment of metastatic tumors while sparing non-tumor cells. Rec ent evidence has revealed that both CD8 cytotoxic T lymphocytes (CTLs) and also CD4 helper T lymphocytes (HTLs) can distinguish post-translat...
Source: Cancer Immunology, Immunotherapy - February 21, 2020 Category: Cancer & Oncology Source Type: research

Nivolumab in patients with metastatic renal cell carcinoma and chronic hepatitis C virus infection
ConclusionsThe efficacy and safety profiles observed in this study support the administration of nivolumab in mRCC patients infected with HCV and warrant further investigation. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 20, 2020 Category: Cancer & Oncology Source Type: research

CD1d expression and invariant natural killer T-cell numbers are reduced in patients with upper gastrointestinal cancers and are further impaired by commonly used chemotherapies
AbstractEsophageal and gastric cancers collectively cause over 1.1 million deaths annually and only 20 –30% of patients respond favorably to current therapies. Cellular therapies using invariant natural killer T (iNKT) cells are showing promise for patients with other cancers; therefore, we investigated if these cells are altered in esophageal and gastric cancer patients. Flow cytometric analysis o f peripheral blood from 139 patients revealed that iNKT cells are depleted from patients with esophageal and gastric adenocarcinoma and esophageal squamous cell carcinoma, both before and after treatment. Interrogation of ...
Source: Cancer Immunology, Immunotherapy - February 20, 2020 Category: Cancer & Oncology Source Type: research

Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients
We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and e...
Source: Cancer Immunology, Immunotherapy - February 20, 2020 Category: Cancer & Oncology Source Type: research

miRNA-5119 regulates immune checkpoints in dendritic cells to enhance breast cancer immunotherapy
This study provides evidence supporting a novel therapeutic approach using miRNA-5119 mimic-engineered DC vaccines to regulate inhibitory receptors and enhance anti-tumor immune response in a mouse model of breast cancer. miRNA/DC-based immunotherapy has potential for advancement to the clinic as a new strategy for DC-based anti-breast cancer immunotherapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 20, 2020 Category: Cancer & Oncology Source Type: research

Development and characterization of a novel anti-OX40 antibody for potent immune activation
AbstractWith the great success of anti-CTLA-4 and anti-PD-1 therapeutics in cancer immunotherapy, tumor necrosis factor receptor superfamily members have been recognized as ideal targets to provide co-stimulatory signals in combination with immune checkpoint blocking antibodies. Among these is OX40 (CD134), a co-stimulatory molecule expressed by activated immune cells. Recently, several anti-OX40 agonistic monoclonal antibodies, pogalizumab as the most advanced, have entered early phase clinical trials. Using a  yeast platform and multiple screening methods, we identified a fully human anti-OX40 antibody (IBI101) with...
Source: Cancer Immunology, Immunotherapy - February 20, 2020 Category: Cancer & Oncology Source Type: research

Predictive value of positron emission tomography for the prognosis of immune checkpoint inhibitors (ICIs) in malignant tumors
This study aimed at investigating the value of applying positron emission tomography (PET) to early predict the effect of immune checkpoint inhibitors (ICIs) in malignant tumors.MethodsElectronic databases MEDLINE/PubMed, EMBASE, and Cochrane Library were searched to identify relevant trials. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The results were analyzed utilizing SPSS 19.0 statistical software. Subgroup analyses were implemented based on primary  tumors, study designs, continents, type of ICIs, evaluation index of PET, and evaluated PET timing.ResultsFifteen studi...
Source: Cancer Immunology, Immunotherapy - February 19, 2020 Category: Cancer & Oncology Source Type: research

Acknowledgement to reviewers
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 18, 2020 Category: Cancer & Oncology Source Type: research

LincRNA-p21 knockdown reversed tumor-associated macrophages function by promoting MDM2 to antagonize* p53 activation and alleviate breast cancer development
AbstractTumor-associated macrophages (TAMs) are important regulators of the complex interplay between immune system and breast cancer. TAMs fuel the cancer progression and metastasis by reprogramming their specific functional phenotype in cancer settings. Therefore, it is important to clarify the mechanisms of shaping specific functional phenotype of macrophages in tumor milieu. LncRNA profiles of TAMs were identified by LncRNA microarray. Flow cytometry was used to detect the surface markers of TAMs. The co-localization among lincRNA-p21, p53 and Mouse Double Minute 2 (MDM2) was identified by FISH probe and immunofluoresc...
Source: Cancer Immunology, Immunotherapy - February 15, 2020 Category: Cancer & Oncology Source Type: research

CIK cell cytotoxicity is a predictive biomarker for CIK cell immunotherapy in postoperative patients with hepatocellular carcinoma
In conclusion, a high cytotoxic activity of CIK cells can serve as a valuable biomarker for adju vant CIK cell immunotherapy of HCC patients after surgery. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 14, 2020 Category: Cancer & Oncology Source Type: research

Co-expression of HLA-I loci improved prognostication in HER2+ breast cancers
AbstractThe underlying basis for cancer immune evasion is important for effective immunotherapy and prognosis in breast cancers. Human leucocyte antigens (HLA)-I comprising three classical antigens (HLA-A, -B and -C) is mandatory for anti-tumor immunity. Its loss occurred frequently in many cancers resulting in effective immune evasion. Most studies examined HLA-I as a whole. Alterations in specific locus could have different clinical ramifications. Hence, we evaluated the expression of the three HLA-I loci in a large cohort of breast cancers. Low expression of HLA-A, -B and -C were found in 71.1%, 66.3%, and 60.2% of the ...
Source: Cancer Immunology, Immunotherapy - February 13, 2020 Category: Cancer & Oncology Source Type: research

CD160 expression on CD8 + T cells is associated with active effector responses but limited activation potential in pancreatic cancer
In this study, we investigated the effects of CD160 on CD8+ T cells in pancreatic cancer. First, we found that the frequency of PD-1+ cells was comparable between CD160+ and CD160−CD8+ T cells, with the former presenting significantly higher PD-1 expression level. In contrast, the frequency of TIM-3+ cells was higher among CD160+ cells but the expression level was comparable between CD160+ and CD160−CD8+ T cells. The IFN- γ and IL-2-expressing CD8+ T cells, directly ex vivo, were highly enriched in the CD160+ subset. However, when CD160+ and CD160−CD8+ T cells were stimulated, the proliferation leve...
Source: Cancer Immunology, Immunotherapy - February 13, 2020 Category: Cancer & Oncology Source Type: research

Immunoregulatory effects of Lurbinectedin in chronic lymphocytic leukemia
In this study, we aimed to evaluate the activity of Lurbinectedin on circulating mononuclear cells from CLL patients and to determine whether Lurbinectedin could affect the cross-talk between B-CLL cells and the tumor microenvironment. We found that Lurbinectedin induced a dose- and time-dependent death in all cell types evaluated, with B cells, monocytes and monocytic myeloid derived suppressor cells (Mo-MDSC) being the most susceptible populations. At sub-apoptotic doses, Lurbinectedin decreased the expression of CCR7 in B-CLL cells and impaired their migration towards CCL19 and CCL21. Furthermore, low concentrations of ...
Source: Cancer Immunology, Immunotherapy - February 13, 2020 Category: Cancer & Oncology Source Type: research

Talimogene laherparepvec treatment to overcome loco-regional acquired resistance to immune checkpoint blockade in tumor stage IIIB –IV M1c melanoma patients
ConclusionT-VEC represents an effective and tolerable treatment option. This is true not only for loco-regionally advanced melanoma patients, but also for patients with stable or regressive systemic metastases who develop loco-regionally acquired resistance upon treatment with immune checkpoint blockade or targeted therapy. A sensible selection of suitable patients seems to be crucial. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 12, 2020 Category: Cancer & Oncology Source Type: research

Tumor mutational load, CD8 + T cells, expression of PD-L1 and HLA class I to guide immunotherapy decisions in NSCLC patients
ConclusionThis proof-of-concept study suggests that a combination of PD-L1 expression, TML, CD8+ T cell infiltration and HLA class-I functions as a better predictive biomarker for response to anti-PD-1 immunotherapy. Consequently, refinement of this set of biomarkers and validation in a larger set of patients is warranted. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 12, 2020 Category: Cancer & Oncology Source Type: research

Human inflammatory dendritic cells in malignant pleural effusions induce Th1 cell differentiation
AbstractDendritic cells are crucial for the initiation and regulation of immune responses against cancer and pathogens. DCs are heterogeneous and highly specialized antigen-presenting cells. Human DCs comprise several subsets with different phenotypes and functional properties. In the steady state, human DC subsets have been well studied. However, the components of DC subsets and their immune functions during the inflamed setting are poorly understood. We identified and characterized DC subsets in the malignant pleural effusions of NSCLC patients. We analyzed the capacity of these DC subsets to induce T-cell differentiatio...
Source: Cancer Immunology, Immunotherapy - February 12, 2020 Category: Cancer & Oncology Source Type: research

Intratumoral injection of hemagglutinating virus of Japan-envelope vector yielded an antitumor effect for advanced melanoma: a phase I/IIa clinical study
AbstractHemagglutinating virus of Japan (HVJ; Sendai virus) is an RNA virus that has cell fusion activity. HVJ-envelope (HVJ-E) is a UV-irradiated HVJ particle that loses viral replication and protein synthesis activity but retains cell fusion activity. We recently reported that HVJ-E has antitumor effects on several types of tumors. Here, we describe the results of a first-in-human phase I/IIa study in patients with advanced melanoma, receiving intratumoral administration of HVJ-E. The primary aim was to evaluate the safety and tolerability of HVJ-E, and the secondary aim was to examine the objective tumor response and an...
Source: Cancer Immunology, Immunotherapy - February 11, 2020 Category: Cancer & Oncology Source Type: research

Activation of TLR4 signaling inhibits progression of osteosarcoma by stimulating CD8-positive cytotoxic lymphocytes
ConclusionTLR4 activation by LPS increased CD8+ cells infiltrating into lung metastases and suppressed OS progression in the mouse model. TLR4 activation may suppress the progression of OS via stimulating CD8+ cells and can be expected as a novel treatment for OS. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 11, 2020 Category: Cancer & Oncology Source Type: research