Efficacy and safety of sintilimab in combination with chemotherapy in previously untreated advanced or metastatic nonsquamous or squamous NSCLC: two cohorts of an open-label, phase 1b study
The objective response rate was 68.4% (95% CI 43.4%, 87.4%) in cohort D and 64.7% (95% CI 38.3%, 85.8%) in cohort E. Neither PD-L1 expression nor tumor mutation b urden value was significantly associated with an improved treatment response. Sintilimab plus chemotherapy exhibited manageable toxicity and an encouraging antitumor activity in patients with nsqNSCLC and sqNSCLC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 26, 2021 Category: Cancer & Oncology Source Type: research

Systematic analysis of immune-related genes based on a combination of multiple databases to build a diagnostic and a prognostic risk model for hepatocellular carcinoma
In this study, we identified the differentially expressed IRGs and analyzed their functions in HCC in a systematic way. Furthermore, we constructed a diagnostic and a prognostic model using multiple statistical methods, and both models had good distinguishing performance, which we verified in several independent datasets. This diagnostic model was also adaptable to proteomic data. The combination of a prognostic risk model and classic clinical staging can effectively distinguish patients in high- and low-risk groups. Furthermore, we systematically explore the differences in the immune microenvironment between the high-risk...
Source: Cancer Immunology, Immunotherapy - February 26, 2021 Category: Cancer & Oncology Source Type: research

Phase I, first-in-human trial of programmed cell death receptor-1 (PD-1) inhibitor, JTX-4014, in adult patients with advanced, refractory, solid tumors
ConclusionsFurther development of JTX-4014 is warranted as a monotherapy or in combination with other innovative cancer therapies.Trial registration numberNCT03790488, December 31 2018. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 26, 2021 Category: Cancer & Oncology Source Type: research

Anti-leukemia effect associated with down-regulated CD47 and up-regulated calreticulin by stimulated macrophages in co-culture
AbstractCD47 is over-expressed in Acute Myeloid Leukemia (AML) and functions as an inhibitory signal, suppressing phagocytosis by binding to signal regulatory protein α (SIRPα) on the surface of macrophages. Inhibition of CD47 restores the immune surveillance of AML cells. However, the inhibition of CD47 in AML by activated macrophages and the subsequent effects on different immune response parameters are not fully understood. Here, we demonstrate the use of a distinct co-culture method to inhibit CD47 and therefore eliminate AML cells by macrophages in vitro. Human chemically induced THP-1 macrophages were act...
Source: Cancer Immunology, Immunotherapy - February 26, 2021 Category: Cancer & Oncology Source Type: research

Anti-tumor and immune modulating activity of T cell induced tumor-targeting effectors (TITE)
AbstractAdoptive transfer of Bispecific antibody Armed activated T cells (BATs) showed promising anti-tumor activity in clinical trials in solid tumors. The cytotoxic activity of BATs occurs upon engagement with tumor cells via the bispecific antibody (BiAb) bridge, which stimulates BATs to release cytotoxic molecules, cytokines, chemokines, and other signaling molecules extracellularly. We hypothesized that the release of BATs Induced Tumor-Targeting Effectors (TITE) by this complex interaction of T cells, bispecific antibody, and tumor cells may serve as a potent anti-tumor and immune-activating immunotherapeutic approac...
Source: Cancer Immunology, Immunotherapy - February 26, 2021 Category: Cancer & Oncology Source Type: research

Downregulated ATP6V1B1 expression acidifies the intracellular environment of cancer cells leading to resistance to antibody-dependent cellular cytotoxicity
AbstractAmong several mechanisms for the resistance of human epidermal growth factor receptor 2-overexpressing (HER2  +) cancer cells to trastuzumab, little is known regarding the mechanism underlying the resistance to trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Cell death due to ADCC is caused by apoptosis of target cells induced by granzymes released from natural killer cells. Because optimal granzyme physiological activity occurs at neutral pH, we assumed that the pH of the intracellular environment influences the cytotoxic effects of granzymes. We established ADCC-resistant cells and co...
Source: Cancer Immunology, Immunotherapy - February 26, 2021 Category: Cancer & Oncology Source Type: research

Comparative assessment of manual chart review and ICD claims data in evaluating immunotherapy-related adverse events
DiscussionExamining gastrointestinal and pulmonary irAEs through the International Classification of Disease (ICD) data leads to underrepresentation of true irAEs and overrepresentation of false irAEs. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 24, 2021 Category: Cancer & Oncology Source Type: research

Interplay of stromal tumor-infiltrating lymphocytes, normal colonic mucosa, cancer-associated fibroblasts, clinicopathological data and the immunoregulatory molecules of patients diagnosed with colorectal cancer
AbstractA total of 94 patients with colorectal cancer (CRC) were included in this study. Lymphocytic infiltration of CD45+ cells in the normal colon was more pronounced than that in the paired tumor stroma (p = 0.0008). The mean immunoscore of CD45+TILs was decreased in CRC compared with the controls (p = 0.0010). The percentage of CD3+ cells was higher in stage II than in stage IV (p = 0.0218) and showed a negative correlation with the TNM classification (r = -0.2867,p = 0.0109). The number of stromal CD4+TILs was higher in stage I than in stage III (p&...
Source: Cancer Immunology, Immunotherapy - February 24, 2021 Category: Cancer & Oncology Source Type: research

Sarcopenia and the risk of adverse events in patients treated with immune checkpoint inhibitors: a systematic review
ConclusionMost of the included studies showed an increased risk of AEs with use of ICIs in cancer patients with sarcopenia, and in the majority of these, the increase was statistically significant. Due to the small number of available studies and the expanding use of ICIs, additional research is warranted. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 24, 2021 Category: Cancer & Oncology Source Type: research

Identification of immune checkpoint and cytokine signatures associated with the response to immune checkpoint blockade in gastrointestinal cancers
AbstractImmune checkpoint blockade (ICB) of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoint pathway has led to unprecedented advances in cancer therapy. However, the overall response rate of anti-PD-1/PD-L1 monotherapy is still unpromising, underscoring the need for predictive biomarkers. In this retrospective study, we collected pretreatment plasma samples from two independent cohorts of patients receiving ICB. To determine whether a signature of plasma cytokines could be associated with therapeutic efficacy, we systemically profiled cytokine clusters and functional groups in the ...
Source: Cancer Immunology, Immunotherapy - February 23, 2021 Category: Cancer & Oncology Source Type: research

Development and validation of a PD-L1/PD-1/CD8 axis-based classifier to predict cancer survival of upper tract urothelial carcinoma after radical nephroureterectomy
AbstractThe expression status of programmed cell death-ligand 1/programmed cell death 1 (PD-L1/PD-1) and the infiltration of CD8+ T cells in tumor tissues are considered to be related to immunotherapy efficacy and patient prognosis. The purpose of this study is to clarify the prognostic value of the PD-L1/PD-1/CD8 axis, and to develop and validate a comprehensive scoring system based on multiple immune variables to predict cancer survival of upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). The immunohistochemical method was used to detect the expression of PD-L1, PD-1, and CD8 in cancer tissu...
Source: Cancer Immunology, Immunotherapy - February 19, 2021 Category: Cancer & Oncology Source Type: research

Heterogeneity of PD-L1 expression between invasive and lepidic components of lung adenocarcinomas
AbstractThe dynamics of PD-L1 expression are poorly understood over the development of lung adenocarcinomas from pre-invasive lesions to fully invasive carcinomas. Given the importance of PD-L1 expression for the selection of patients to receive immunotherapy in the metastatic setting and possibly in the neoadjuvant setting, we sought to evaluate the agreement of PD-L1 expression in invasive and lepidic components of resected tumor specimens. We stained 86 adenocarcinomas for PD-L1 using the SP263 clone. We assessed the agreement of PD-L1 expression by tumor cells and immune cells between lepidic and invasive components. W...
Source: Cancer Immunology, Immunotherapy - February 18, 2021 Category: Cancer & Oncology Source Type: research

Correction to: In-depth characterization of the tumor microenvironment in central nervous system lymphoma reveals implications for immune-checkpoint therapy
The original version of this article unfortunately contained a mistake. Paul Clement and Steven De Vleeschouwer were not listed among the authors. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 17, 2021 Category: Cancer & Oncology Source Type: research

Prognostic role of the systemic immune –inflammation index in upper tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration
AbstractPurposeTo investigate the prognostic role of the preoperative systemic immune –inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU).Materials and methodsWe retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count  × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performe...
Source: Cancer Immunology, Immunotherapy - February 16, 2021 Category: Cancer & Oncology Source Type: research

Transcriptome of CD8 + tumor-infiltrating T cells: a link between diabetes and colorectal cancer
AbstractThere is an increased risk of colorectal cancer (CRC) development in patients with non-insulin-dependent type 2 diabetes. CD8+ T cells have been implicated in diabetes and are crucial for anti-tumor immunity. However, transcriptomic profiling for CD8+ T cells from CRC diabetic patients has not been explored. We performed RNA sequencing and compared transcriptomic profiles of CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) in CRC diabetic patients with CRC nondiabetic patients. We found that genes associated with ribogenesis, epigenetic regulations, oxidative phosphorylation and cell cycle arrest were upregul...
Source: Cancer Immunology, Immunotherapy - February 13, 2021 Category: Cancer & Oncology Source Type: research

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial
ConclusionIn this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 12, 2021 Category: Cancer & Oncology Source Type: research

PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung
In conclusion, PD-L1 amplification correlates with PD-L1 expression in squamous cell cancer and was associated with an immune cell rich tumor phenotype. The correlative findings help to understand the role of PD-L1 amplification as an important immune escape mechanism in NSCLC an d suggest the need to further evaluate PD-L1 amplification as predictive biomarker for checkpoint inhibitor therapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 12, 2021 Category: Cancer & Oncology Source Type: research

Novel roles of VAT1 expression in the immunosuppressive action of diffuse gliomas
AbstractStandard treatment regimen of gliomas has almost reached a bottleneck in terms of survival benefit. Immunotherapy has been explored and applied in glioma treatment. Immunosuppression, as a hallmark of glioma, could be alleviated by inhibiting certain abnormally expressed biomarkers. Here, transcriptome data of 325 whole grade gliomas were collected from the CGGA database. The TCGA RNA sequencing database was used for validation. Western blot was used to verify the expression level of VAT1 on cellular level. The results showed that the expression of VAT1 was positively correlated with the grades of glioma as classif...
Source: Cancer Immunology, Immunotherapy - February 12, 2021 Category: Cancer & Oncology Source Type: research

Immune-related adverse events: promising predictors for efficacy of immune checkpoint inhibitors
This study was designed to investigate the correlation between immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs) and corresponding efficacy, and to explore the potential of predicting the efficacy of ICIs via irAEs.MethodsElectronic databases including PubMed, Embase, Cochrane Library, CNKI and Wanfang were applied to search for relevant studies. The primary endpoint was overall survival (OS) or progression-free survival (PFS), and the secondary endpoint was objective response rate (ORR). Stratification analyses were conducted according to the type of irAEs and ICIs, region of studies and primary...
Source: Cancer Immunology, Immunotherapy - February 12, 2021 Category: Cancer & Oncology Source Type: research

Regulatory T cells promote glioma cell stemness through TGF- β–NF-κB–IL6–STAT3 signaling
AbstractGlioma stem cells (GSCs) contribute to the malignant growth of glioma, but little is known about the interaction between GSCs and tumor microenvironment. Here, we found that intense infiltration of regulatory T cells (Tregs) facilitated the qualities of GSCs through TGF- β secretion that helped coordinately tumor growth. Mechanistic investigations indicated that TGF-β acted on cancer cells to induce the core cancer stem cell-related genes CD133, SOX2, NESTIN, MUSASHI1 and ALDH1A expression and spheres formation via NF-κB–IL6–STAT3 signaling pathway, resulting in the increased cancer stem...
Source: Cancer Immunology, Immunotherapy - February 12, 2021 Category: Cancer & Oncology Source Type: research

Metabolic profiles of regulatory T cells in the tumour microenvironment
AbstractMetabolic reprogramming of cancer cells generates a tumour microenvironment (TME)  characterised by nutrient restriction, hypoxia, acidity and oxidative stress. While these conditions are unfavourable for infiltrating effector T cells, accumulating evidence suggests that regulatory T cells (Tregs) continue to exert their immune-suppressive functions within the TME. The advantag es of Tregs within the TME stem from their metabolic profile. Tregs rely on oxidative phosphorylation for their functions, which can be fuelled by a variety of substrates. Even though Tregs are an attractive target to augment anti-...
Source: Cancer Immunology, Immunotherapy - February 12, 2021 Category: Cancer & Oncology Source Type: research

The liposome of trehalose dimycolate extracted from M.  bovis BCG induces antitumor immunity via the activation of dendritic cells and CD8 + T cells
AbstractIntravesicalBovis bacillus Calmette-Gu érin (BCG) therapy is the most effective immunotherapy for bladder cancer, but it sometime causes serious side effects because of its inclusion of live bacteria. It is necessary to develop a more active but less toxic immunotherapeutic agent. Trehalose 6,6′-dimycolate (TDM), the most abundant hyd rophobic glycolipid of the BCG cell wall, has been reported to show various immunostimulatory activities such as granulomagenesis and adjuvant activity. Here, we developed cationic liposomes incorporating TDM purified fromMycobacterium bovis BCG Connaught, and we investig...
Source: Cancer Immunology, Immunotherapy - February 11, 2021 Category: Cancer & Oncology Source Type: research

The cytokine milieu compromises functional capacity of tumor-infiltrating plasmacytoid dendritic cells in HPV-negative but not in HPV-positive HNSCC
AbstractPlasmacytoid dendritic cells (pDCs) are the most potent type I interferon-producing cells and play an important role in antiviral immunity. Tumor-infiltrating pDCs were shown to be predominantly pro-tumorigenic, with reduced ability to produce interferon alpha (IFN α) and confirmed capacity to prime regulatory T cells (Tregs) by the ICOS/ICOS-L pathway. Because a significant number of HNSCCs are induced by human papillomaviruses and show markedly different immune profiles than non-virally induced tumors, we compared the phenotype and functional capacity of HN SCC-infiltrating pDCs to the HPV status of the tum...
Source: Cancer Immunology, Immunotherapy - February 11, 2021 Category: Cancer & Oncology Source Type: research

Anlotinib combined with PD-1 blockade for the treatment of lung cancer: a real-world retrospective study in China
This study evaluated the efficacy and safety of anlotinib combined with programmed cell death protein 1 (PD-1) blockade for the treatment of small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC).Patients and methodsSCLC (n = 28) and NSCLC (n = 177) patients who received treatment at Hunan Cancer Hospital between June 1, 2019, and July 1, 2020, were retrospectively analyzed. Progression-free survival (PFS) and treatment responses were compared among patients who received combination therapy of anlotinib plus PD-1 inhibitor, or monot herapy of either chemotherapy or PD-1 inhibitor. ...
Source: Cancer Immunology, Immunotherapy - February 10, 2021 Category: Cancer & Oncology Source Type: research

Enhanced anti-tumor efficacy of IL-7/CCL19-producing human CAR-T cells in orthotopic and patient-derived xenograft tumor models
In this study, for a preclinical evaluation preceding clinical application, we further explored the po tential of IL-7/CCL19-producing human CAR-T cells using models that mimic the clinical features of solid tumors. Human anti-mesothelin CAR-T cells producing human IL-7/CCL19 achieved complete eradication of orthotopic pre-established malignant mesothelioma and prevented a relapse of tumors with down regulated antigen expression. Moreover, mice with patient-derived xenograft of mesothelin-positive pancreatic cancers exhibited significant inhibition of tumor growth and prolonged survival following treatment with IL-7/CCL19-...
Source: Cancer Immunology, Immunotherapy - February 8, 2021 Category: Cancer & Oncology Source Type: research

Normalization of electroretinogram and symptom resolution of melanoma-associated retinopathy with negative autoantibodies after treatment with programmed death-1 (PD-1) inhibitors for metastatic melanoma
We report the first case to our knowledge with subjective resolution of visual symptoms and objective evidence of normalization of electroretinogram of MAR with undetectable autoantibodies after ad ministration of programmed death-1 (PD-1) inhibitor (pembrolizumab) without the use of surgical reduction or systemic immunosuppression. This case highlights the potential improvement and resolution of negative autoantibody MAR with the use of PD-1 inhibitors and emphasizes the importance of multidi sciplinary approach and team discussion to avoid interventions that can decrease immunotherapy-mediated anti-tumor effect. (Source:...
Source: Cancer Immunology, Immunotherapy - February 5, 2021 Category: Cancer & Oncology Source Type: research

Interleukin-7-loaded oncolytic adenovirus improves CAR-T cell therapy for glioblastoma
ConclusionsOur results indicated that oAD-IL7 is a promising auxiliary therapy to improve the therapeutic efficacy of B7H3-CAR-T in glioblastoma by providing the activating signals for tumor-infiltrating T cells. Our results also lay the basis for the future clinical trials for the combination of IL7-loaded oncolytic adenovirus and CAR-T therapy for glioblastoma. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - February 4, 2021 Category: Cancer & Oncology Source Type: research

Platelet-expressed immune checkpoint regulator GITRL in breast cancer
AbstractOwing to their key role in several diseases including cancer, activating and inhibitory immune checkpoint molecules are increasingly exploited as targets for immunotherapy. Recently, we demonstrated that platelets, which largely influence tumor progression and immune evasion, functionally express the ligand of the checkpoint molecule GITR. This immunoreceptor modulates effector functions of T cells and NK cells with its function varying dependent on cellular context and activation state. Here, we provide a comparative analysis of platelet-derived GITRL (pGITRL) in breast cancer patients and healthy volunteers. The ...
Source: Cancer Immunology, Immunotherapy - February 4, 2021 Category: Cancer & Oncology Source Type: research

IL-36 γ-armed oncolytic virus exerts superior efficacy through induction of potent adaptive antitumor immunity
In this study, we aimed to apply the cytokine IL-36γ to cancer immunotherapy by constructing new oncolytic vaccinia viruses (OV) expressing interleukin-36γ (IL-36γ-OVs), leveraging unique synergism between OV and IL-36γ’s ability to promote antitumor adaptive immunity and modulate tumor microenvironment (TME). IL-36γ-OV had dramatic therapeutic efficacies in multiple murine tumor models, frequently leading to complete cancer eradication in large fractions of mice. Mechanistically, IL-36-γ-armed OV induced infiltration of lymphocytes and dendritic cells, decreased myeloid-derived su...
Source: Cancer Immunology, Immunotherapy - February 4, 2021 Category: Cancer & Oncology Source Type: research

Mast cell proliferation in the cerebrospinal fluid after intraventricular administration of anti-B7H3 immunotherapy
AbstractOmburtamab is a B7H3-specific murine monoclonal antibody. B7H3 (CD 276) is a member of the B7 family of immune checkpoint co-inhibitory receptors overexpressed on many human malignancies. Radioimmunotherapy with124I- or131I-omburtamab administered in the cerebrospinal fluid (CSF), intraperitoneal or intratumoral cavity is currently under investigation for the treatment of CNS malignancies. The immunologic effects of anti-B7H3 therapy are not fully elucidated. A 6-year-old male was diagnosed with metastates of neuroblastoma to the received intraventricular131I-omburtamab on an IRB-approved protocol. A treatment cycl...
Source: Cancer Immunology, Immunotherapy - February 3, 2021 Category: Cancer & Oncology Source Type: research

Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment
AbstractMetabolic dysregulation in the hypoxic tumor microenvironment (TME) is considered as a hallmark of solid tumors, leading to changes in biosynthetic pathways favoring onset, survival and proliferation of malignant cells. Within the TME, hypoxic milieu favors metabolic reprogramming of tumor cells, which subsequently affects biological properties of tumor-infiltrating immune cells. T regulatory cells (Tregs), including both circulating and tissue-resident cells, are particularly susceptible to hypoxic metabolic signaling that can reprogram their biological and physicochemical properties. Furthermore, metabolic reprog...
Source: Cancer Immunology, Immunotherapy - February 3, 2021 Category: Cancer & Oncology Source Type: research

Tumor mutation score is more powerful than tumor mutation burden in predicting response to immunotherapy in non-small cell lung cancer
AbstractTumor mutation burden (TMB) predicts response to immunotherapy in non-small cell lung cancer (NSCLC). The current TMB evaluation is expensive and not satisfactory. Here, novel tumor mutation score (TMS) was defined as the number of genes with mutations in candidate genes and compared with TMB and PD-L1 in 240 NSCLC patients and validated in 34 NSCLC patients. Eighteen genes were significantly associated with longer progression-free survival (PFS) or better response. The number of mutated genes within 18 favorable genes were defined as TMS18. TMS18 (HR  = 0.307,P 
Source: Cancer Immunology, Immunotherapy - February 3, 2021 Category: Cancer & Oncology Source Type: research

CD30 + OX40 + Treg is associated with improved overall survival in colorectal cancer
AbstractRegulatory T cells (Tregs) are often enriched in tumors, where their immunosuppressive function has a key role in tumor persistence and progression. In colorectal cancer (CRC), however, Tregs are frequently associated with an improved clinical outcome. Tumor-infiltrating Tregs have been shown to exhibit a distinct signature comprising the co-stimulatory molecules (OX40, 4-1BB), cytokine receptors (IL1R2, IL21R, CCR8, CD30), and co-inhibitory molecules (PD-L1, TIGIT). Here, we showed by flow cytometry that circulating CD45RO+ Tregs from patients with CRC (n = 25) have elevated CD30 and OX40 expression ...
Source: Cancer Immunology, Immunotherapy - February 2, 2021 Category: Cancer & Oncology Source Type: research

The surgical perspective in neoadjuvant immunotherapy for resectable non-small cell lung cancer
ConclusionsPulmonary resection after neoadjuvant immunotherapy or chemo-immunotherapy for resectable NSCLC appears to be safe with low operative mortality and morbidity rate in the current population. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 29, 2021 Category: Cancer & Oncology Source Type: research

The predictive value of body mass index on prognosis and adverse events of cancers treated with immunotherapy: a systematic review and meta-analysis
ConclusionIn general, high BMI was correlated with improved OS and PFS in patients treated with immunotherapy along with a high risk of irAEs. However, discrepant findings from subgroup analyses urgently call for further analysis. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 29, 2021 Category: Cancer & Oncology Source Type: research

Interleukin 17A promotes cell migration, enhances anoikis resistance, and creates a microenvironment suitable for triple negative breast cancer tumor metastasis
ConclusionWe conclude that IL-17A promotes migratory and angiogenic activity in tumors, enhances anoikis resistance, and modulates the immune landscape of the tumor microenvironment such changes favor cancer metastasis. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 29, 2021 Category: Cancer & Oncology Source Type: research

Activity of tumor-associated macrophage depletion by CSF1R blockade is highly dependent on the tumor model and timing of treatment
AbstractTumor-associated macrophages (TAMs) are abundant in solid tumors where they exhibit immunosuppressive and pro-tumorigenic functions. Inhibition of TAM proliferation and survival through CSF1R blockade has been widely explored as a cancer immunotherapy. To further define mechanisms regulating CSF1R-targeted therapies, we systematically evaluated the effect of anti-CSF1R treatment on tumor growth and tumor microenvironment (TME) inflammation across multiple murine models. Despite substantial macrophage depletion, anti-CSF1R had minimal effects on the anti-tumor immune response in mice bearing established tumors. In c...
Source: Cancer Immunology, Immunotherapy - January 29, 2021 Category: Cancer & Oncology Source Type: research

Support of BCP-ALL-cells by autologous bone marrow Th-cells involves induction of AID expression but not widespread AID off-target mutagenesis
AbstractB-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common childhood malignancy. The two-step BCP-ALL pathogenesis requires in utero-induced chromosomal aberrations and additional mutagenic events for overt leukemia. In mouse models, activation-induced cytidine deaminase (AID/AICDA) was suggested to contribute to BCP-ALL pathogenesis by off-target mutagenic activity. The role of AID in patients, however, remains unclear. Moreover, AID is usually not expressed in precursor B-cells but in germinal center B-cells, where it is induced upon T-helper (Th) cell stimulation. We have previously demonstrated ...
Source: Cancer Immunology, Immunotherapy - January 28, 2021 Category: Cancer & Oncology Source Type: research

A critical role of STING-triggered tumor-migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment
AbstractStimulator of interferon genes (STING) contributes to anti-tumor immunity by activating antigen-presenting cells and inducing mobilization of tumor-specific T cells. A role for tumor-migrating neutrophils in the anti-tumor effect of STING-activating therapy has not been defined. We used mouse tumor transplantation models for assessing neutrophil migration into the tumor triggered by intratumoral treatment with STING agonist, 2 ′3′-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Intratumoral STING activation with cGAMP enhanced neutrophil migration into the tumor in an NF-κB/CXCL1/2...
Source: Cancer Immunology, Immunotherapy - January 28, 2021 Category: Cancer & Oncology Source Type: research

Novel Kras -mutant murine models of non-small cell lung cancer possessing co-occurring oncogenic mutations and increased tumor mutational burden
AbstractConditional genetically engineered mouse models (GEMMs) of non-small cell lung cancer (NSCLC) harbor common oncogenic driver mutations of the disease, but in contrast to human NSCLC these models possess low tumor mutational burden (TMB). As a result, these models often lack tumor antigens that can elicit host adaptive immune responses, which limits their utility in immunotherapy studies. Here, we establishKras-mutant murine models of NSCLC bearing the common driver mutations associated with the disease and increased TMB, by in vitro exposure of cell lines derived from GEMMs of NSCLC [KrasG12D (K),KrasG12DTp53&minus...
Source: Cancer Immunology, Immunotherapy - January 28, 2021 Category: Cancer & Oncology Source Type: research

T-VEC for stage IIIB-IVM1a melanoma achieves high rates of complete and durable responses and is associated with tumor load: a clinical prediction model
ConclusionsThis study shows that intralesional T-VEC monotherapy is able to achieve high complete and durable responses. The prediction model shows that use of T-VEC in patients with less tumor burden is associated with better outcomes, suggesting use earlier in the course of the disease. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 28, 2021 Category: Cancer & Oncology Source Type: research

Single-cell RNA sequencing reveals cellular and molecular immune profile in a Pembrolizumab-responsive PD-L1-negative lung cancer patient
In this study, we aimed to explore the underlying cellular and molecular characteristics via single-cell sequencing. Before and after treatment with Pembrolizumab, peripheral blood mononuclear cells (PBMCs) were isolated via Ficoll gradient. Thereafter, single-cell RNA sequencing was performed, and clinical significance was validated with The Cancer Genome Atlas (TCGA) cohort. All 3423 cells of 16 clusters were classified into eight cell types, including NKG7+ T, NKG7+ NK, Na ïve T, CDC1C+ dendritic cells, CD8+ T cells, B cells, macrophages and erythrocytes. Cell proportion, the clinical significance of differentially...
Source: Cancer Immunology, Immunotherapy - January 27, 2021 Category: Cancer & Oncology Source Type: research

PD-1/PD-L1 checkpoint inhibitors in combination with olaparib display antitumor activity in ovarian cancer patient-derived three-dimensional spheroid cultures
This study examined the effectiveness of detecting patient-specific immune-related activity in OC using three-dimensional (3D) spheroids. Immune-related cell composition  and PD-1/PD-L1 expression status were evaluated using cells dissociated from fresh OC tissue from two patients prior to and following 3D culture. The patient sample with the greatest increase in the proportion of PD-L1 + cells also possessed more activated cytotoxic T cells and mature DCs comp ared to the other patient sample. Upon cytokine stimulation, patient samples demonstrated increases in cytotoxic T cell activation and DC major h...
Source: Cancer Immunology, Immunotherapy - January 25, 2021 Category: Cancer & Oncology Source Type: research

miR-34a induces immunosuppression in colorectal carcinoma through modulating a SIRT1/NF- κB/B7-H3/TNF-α axis
In conclusion, our study uncovered an etiological mechanism underlying miR-34a-mediated CRC immune evasion through inhibition of SIRT1 and promotion of NF- κB/B7-H3/TNF-α axis. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 25, 2021 Category: Cancer & Oncology Source Type: research

LncRNA UCA1 attenuated the killing effect of cytotoxic CD8  + T cells on anaplastic thyroid carcinoma via miR-148a/PD-L1 pathway
ConclusionUCA1 attenuated the killing effect of cytotoxic CD8  + T cells on ATC cells through the miR-148a/PD-L1 pathway. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 24, 2021 Category: Cancer & Oncology Source Type: research

Immunotherapy response modeling by ex-vivo organ culture for lung cancer
AbstractOne of the major hurdles for the advancement of cancer immunotherapy is lack of robust, accessible experimental models. We aimed to produce an ex-vivo organ culture (EVOC) model of immunotherapy for non-small cell lung cancer (NSCLC). Freshly resected early stage tumors were collected from the operating room, fragmented to clusters  
Source: Cancer Immunology, Immunotherapy - January 23, 2021 Category: Cancer & Oncology Source Type: research

Cytokine changes during immune-related adverse events and corticosteroid treatment in melanoma patients receiving immune checkpoint inhibitors
ConclusionsBaseline levels of certain cytokines correlate with specific irAEs in melanoma patients receiving ICIs. irAEs drive a concordant pattern of cytokine fold-change, which is disrupted by corticosteroid treatment. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 22, 2021 Category: Cancer & Oncology Source Type: research

Pembrolizumab-induced immune-mediated fatal colitis with concurrent giardia infection
We present the first case of pembrolizumab-induced fatal colitis with concurrent Giardia infection in a patient with metastatic ovarian cancer. A 47-year-old woman with metastatic ovarian cancer who was being treated with pembrolizumab admitted to our clinic complaining of persisting bloody diarrhoea. Her stool antigen test was positive for Giardia. The patient received metronidazole. A colonoscopy with mucosal biopsy was performed upon no clinical or laboratory improvement. Colonoscopy detected deep exudative ulcers in sigmoid colon and rectum. The cytopathological evaluation revealed immune-mediated ischemic colitis. The...
Source: Cancer Immunology, Immunotherapy - January 22, 2021 Category: Cancer & Oncology Source Type: research

Preexisting autoimmune disease and immune-related adverse events associated with anti-PD-1 cancer immunotherapy: a national case series from the Canadian Research Group of Rheumatology in Immuno-Oncology
ConclusionPAD exacerbations in the context of ICI treatment are common, although generally mild, and occur despite background immunosuppression. Exacerbations are more frequent and severe in patients on more intensive immunosuppressive therapies pre-immunotherapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - January 20, 2021 Category: Cancer & Oncology Source Type: research

Tumor-draining lymph nodes are survival niches that support T cell priming against lymphatic transported tumor antigen and effects of immune checkpoint blockade in TNBC
AbstractTriple negative breast cancer (TNBC) is a significant clinical problem to which immunotherapeutic strategies have been applied with limited success. Using the syngeneic E0771 TNBC mouse model, this work explores the potential for antitumor CD8+ T cell immunity to be primed extratumorally in lymphoid tissues and therapeutically leveraged. CD8+ T cell viability and responses within the tumor microenvironment (TME) were found to be severely impaired, effects coincident with local immunosuppression that is recapitulated in lymphoid tissues in late stage disease. Prior to onset of a locally suppressed immune microenviro...
Source: Cancer Immunology, Immunotherapy - January 18, 2021 Category: Cancer & Oncology Source Type: research