The human anti-CD40 agonist antibody mitazalimab (ADC-1013; JNJ-64457107) activates antigen-presenting cells, improves expansion of antigen-specific T cells, and enhances anti-tumor efficacy of a model cancer vaccine in vivo
AbstractNon-responders to checkpoint inhibitors generally have low tumor T cell infiltration and could benefit from immunotherapy that activates dendritic cells, with priming of tumor-reactive T cells as a result. Such therapies may be augmented by providing tumor antigen in the form of cancer vaccines. Our aim was to study the effects of mitazalimab (ADC-1013; JNJ-64457107), a human anti-CD40 agonist IgG1 antibody, on activation of antigen-presenting cells, and how this influences the priming and anti-tumor potential of antigen-specific T cells, in mice transgenic for human CD40. Mitazalimab activated splenic CD11c+ MHCII...
Source: Cancer Immunology, Immunotherapy - May 5, 2021 Category: Cancer & Oncology Source Type: research

Human hydatid cyst fluid-induced therapeutic anti-cancer immune responses via NK1.1 + cell activation in mice
AbstractEchinococcus granulosus is a cestode parasite which causes cystic echinococcosis disease. Previously we observed that vaccination withE. granulosus antigens from human hydatid cyst fluid (HCF) significantly inhibits colon cancer growth. In the present work, we evaluate the anti-tumor immune response induced by human HCF against LL/2 lung cancer in mice. HCF vaccination protected from tumor growth, both in prophylactic and therapeutic settings, and significantly increased mouse survival compared to control mice. Considering that tumor-associated carbohydrate antigens are expressed inE. granulosus, we oxidized termin...
Source: Cancer Immunology, Immunotherapy - May 4, 2021 Category: Cancer & Oncology Source Type: research

CD38 identifies pre-activated CD8+ T cells which can be reinvigorated by anti-PD-1 blockade in human lung cancer
ConclusionsOur findings demonstrate that CD38 expression defines a subset of CD8+ T cells enriched in tumors of NSCLC which have paradoxical phenotypes and response to anti-PD-1. Our results suggest a pre-priming of these cells is may exist in tumor and consequentially facilitate it acquiring both anti-tumor potency and exhausted phenotype which can be reinvigorated by PD-1 blockade. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 2, 2021 Category: Cancer & Oncology Source Type: research

A novel immune-related gene-based prognostic signature to predict biochemical recurrence in patients with prostate cancer after radical prostatectomy
AbstractAccumulating evidences indicates that the immune landscape signature dramatically correlates with tumorigenesis and prognosis of prostate cancer (PCa). Here, we identified a novel immune-related gene-based prognostic signature (IRGPS) to predict biochemical recurrence (BCR) after radical prostatectomy. We also explored the correlation between IRGPS and tumor microenvironment. We identified an IRGPS consisting of seven immune-related genes (PPARGC1A,AKR1C2,COMP,EEF1A2,IRF5,NTM, andTPX2) that were related to the BCR-free survival of PCa patients. The high-risk patients exhibited a higher fraction of regulatory T cell...
Source: Cancer Immunology, Immunotherapy - May 2, 2021 Category: Cancer & Oncology Source Type: research

Immunotherapy in nonsmall-cell lung cancer: current status and future prospects for liquid biopsy
AbstractImmunotherapy has been one of the great advances in the recent years for the treatment of advanced tumors, with nonsmall-cell lung cancer (NSCLC) being one of the cancers that has benefited most from this approach. Currently, the only validated companion diagnostic test for first-line immunotherapy in metastatic NSCLC patients is testing for programmed death ligand 1 (PD-L1) expression in tumor tissues. However, not all patients experience an effective response with the established selection criteria and immune checkpoint inhibitors (ICIs). Liquid biopsy offers a noninvasive opportunity to monitor disease in patien...
Source: Cancer Immunology, Immunotherapy - April 17, 2021 Category: Cancer & Oncology Source Type: research

Stress relief for cancer immunotherapy: implications for the ER stress response in tumor immunity
AbstractThe solid tumor microenvironment is replete with factors that present a stress to infiltrating immune cells. Endoplasmic reticulum (ER) stress sensor PKR-like ER kinase (PERK) is primed to sense and respond to the burden of misfolded proteins in the ER lumen induced by cell stressors. PERK has documented roles as a master regulator of acute and chronic responses to cell stress as well as in the regulation of cell metabolism. Here, we provide an overview of the roles of PERK based on what is known and remains to be tested in immune cells in tumors and impacts on tumor control. PERK is one of several ER kinases able ...
Source: Cancer Immunology, Immunotherapy - April 17, 2021 Category: Cancer & Oncology Source Type: research

Nivolumab for esophageal squamous cell carcinoma and the predictive role of PD-L1 or CD8 expression in its therapeutic effect
ConclusionsNivolumab is a valuable option at subsequent treatment lines for patients with advanced ESCC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 17, 2021 Category: Cancer & Oncology Source Type: research

Characterization of the tumor immune microenvironment in human papillomavirus-positive and -negative head and neck squamous cell carcinomas
AbstractApproximately 15% of advanced head and neck squamous cell carcinomas (HNSCC) respond to anti-PD-(L)1 monotherapies. Tumor PD-L1 expression and human papillomavirus (HPV) status have been proposed as biomarkers to identify patients likely to benefit from these treatments. We aimed to understand the potential immune effects of HPV in HNSCC and to characterize additional potentially targetable immune-regulatory pathways in primary, treatment-na ïve tumors. CD3, CD4, CD8, CD20, CD68, FoxP3, PD-1, PD-L2, LAG-3, IDO-1, and GITR cell densities were determined in 27 HNSCC specimens. IHC for PD-L1 assessed percentage o...
Source: Cancer Immunology, Immunotherapy - April 17, 2021 Category: Cancer & Oncology Source Type: research

CD1d expression in glioblastoma is a promising target for NKT cell-based cancer immunotherapy
AbstractGlioblastoma is the most common and aggressive type of brain tumor with high recurrence and fatality rates. Although various therapeutic strategies have been explored, there is currently no effective treatment for glioblastoma. Recently, the number of immunotherapeutic strategies has been tested for malignant brain tumors. Invariant natural killer T (iNKT) cells play an important role in anti-tumor immunity. To address if iNKT cells can target glioblastoma to exert anti-tumor activity, we assessed the expression of CD1d, an antigen-presenting molecule for iNKT cells, on glioblastoma cells. Glioblastoma cells from 1...
Source: Cancer Immunology, Immunotherapy - April 17, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Effect of chemoradiotherapy on the proportion of circulating lymphocyte subsets in patients with limited ‑stage small cell lung cancer
A correction to this paper has been published: https://doi.org/10.1007/s00262-021-02929-0 (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 16, 2021 Category: Cancer & Oncology Source Type: research

Mannan-BAM, TLR ligands, and anti-CD40 immunotherapy in established murine pancreatic adenocarcinoma: understanding therapeutic potentials and limitations
AbstractPancreatic adenocarcinoma is one of the leading causes of cancer-related deaths, and its therapy remains a challenge. Our proposed therapeutic approach is based on the intratumoral injections of mannan-BAM, toll-like receptor ligands, and anti-CD40 antibody (thus termed MBTA therapy), and has shown promising results in the elimination of subcutaneous murine melanoma, pheochromocytoma, colon carcinoma, and smaller pancreatic adenocarcinoma (Panc02). Here, we tested the short- and long-term effects of MBTA therapy in established subcutaneous Panc02 tumors two times larger than in previous study and bilateral Panc02 m...
Source: Cancer Immunology, Immunotherapy - April 15, 2021 Category: Cancer & Oncology Source Type: research

Complete rejection of large established breast cancer by local immunochemotherapy with T cell activation against neoantigens
AbstractCancer immunotherapies, including immune checkpoint blockage and adoptive transfer of CAR-T cells, have achieved historical successes for many kinds of malignancy. However, a minority of patients survive long term over 5  years without relapse, perhaps owing to tumor heterogeneity and potent immunosuppression in the tumor microenvironment. Here, using an established mouse tumor model of triple-negative 4T1 breast cancer, we show that local immunochemotherapy triggers powerful local and systemic antitumor immunity. Paraneoplastic injection of CpG, α-OX40, and anthracycline completely eliminated both local...
Source: Cancer Immunology, Immunotherapy - April 14, 2021 Category: Cancer & Oncology Source Type: research

RB1CC1 functions as a tumor-suppressing gene in renal cell carcinoma via suppression of PYK2 activity and disruption of TAZ-mediated PDL1 transcription activation
AbstractRb1-inducible coiled-coil 1 (RB1CC1) has been demonstrated to function as an inhibitor of proline-rich/Ca-activated tyrosine kinase 2 (PYK2) by binding to the kinase domain of PYK2, which promotes the proliferation, invasion, and migration of renal cell carcinoma (RCC) cells. Additionally, in breast cancer, PYK2 positively regulates the expression of transcriptional co-activator with PDZ-binding motif (TAZ) which in turn can enhance PDL1 levels in breast and lung cancer cells. The current study was performed to decipher the impact of RB1CC1 in the progression of RCC via regulation of the PYK2/TAZ/PDL1 signaling axi...
Source: Cancer Immunology, Immunotherapy - April 10, 2021 Category: Cancer & Oncology Source Type: research

Diacylglycerol kinase α inhibition cooperates with PD-1-targeted therapies to restore the T cell activation program
ConclusionsOur results indicate that DGKα inhibition could provide an important mechanism to revert exhausted T lymphocyte phenotypes and thus favor proper anti-tumor T cell responses. The cooperative effect observed after PD-1/PD-L1 and DGKα blockade offers a promising strategy to improve the efficacy of immunotherapy in the treatment of cancer. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 10, 2021 Category: Cancer & Oncology Source Type: research

First time intravesically administered trifunctional antibody catumaxomab in patients with recurrent non-muscle invasive bladder cancer indicates high tolerability and local immunological activity
AbstractTransurethral resection of the tumor (TUR-B) followed by adjuvant intravesical treatment with cytostatic drugs or Bacillus Calmette –Guérin (BCG) as standard therapy of non-muscle-invasive bladder cancer (NMIBC) is associated with a high recurrence rate of about 60–70%, considerable side effects and requires close monitoring. Alternative treatment options are warranted. Two patients with epithelial cell adhesion molecule (E pCAM)-positive recurrent non-muscle invasive bladder cancer were treated the first time by an intravesical administration of the trifunctional bispecific EpCAM targeting antib...
Source: Cancer Immunology, Immunotherapy - April 10, 2021 Category: Cancer & Oncology Source Type: research

Tumour draining lymph node-generated CD8 T cells play a role in controlling lung metastases after a primary tumour is removed but not when adjuvant immunotherapy is used
AbstractSurgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival and future response to immune checkpoint blockade treatment. This project investigates cancer surgery, lymphadenectomy, onset of metastatic disease, and response to immunotherapy in a novel model that closely reflects the clinical setting. In a murine metastatic lung canc...
Source: Cancer Immunology, Immunotherapy - April 9, 2021 Category: Cancer & Oncology Source Type: research

Modeling human tumor-immune environments in vivo for the preclinical assessment of immunotherapies
AbstractDespite the significant contributions of immunocompetent mouse models to the development and assessment of cancer immunotherapies, they inadequately represent the genetic and biological complexity of corresponding human cancers. Immunocompromised mice reconstituted with a human immune system (HIS) and engrafted with patient-derived tumor xenografts are a promising novel preclinical model for the study of human tumor-immune interactions. Whilst overcoming limitations of immunocompetent models, HIS-tumor models often rely on reconstitution with allogeneic immune cells, making it difficult to distinguish between anti-...
Source: Cancer Immunology, Immunotherapy - April 8, 2021 Category: Cancer & Oncology Source Type: research

CMTM6 expression in M2 macrophages is a potential predictor of PD-1/PD-L1 inhibitor response in colorectal cancer
ConclusionsCMTM6 expression in M2 macrophages may predict the PD-1/PD-L1 inhibitor response rate in CRC patients more accurately than dMMR/microsatellite instability-high (MSI-H) status. It can also identify pMMR CRC patients who could benefit from PD-1/PD-L1 inhibitors. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 5, 2021 Category: Cancer & Oncology Source Type: research

Enhancement of innate and adaptive anti-tumor immunity by serum obtained from vascular photodynamic therapy-cured BALB/c mouse
AbstractPhotodynamic therapy (PDT) is a clinically approved treatment for various types of cancer. Besides killing the tumor cells directly, PDT has also been reported to trigger anti-tumor immunity. In our previous study, BAM-SiPc-based PDT was shown to induce immunogenic cell death on CT26 murine colon tumor cells in vitro. Using the BALB/c mouse animal model and a vascular-PDT (VPDT) approach, it could also eradicate tumor in  ∼ 70% of tumor-bearing mice and elicit an anti-tumor immune response. In the present study, the serum obtained from the VPDT-cured mice was studied and found to possess various i...
Source: Cancer Immunology, Immunotherapy - April 5, 2021 Category: Cancer & Oncology Source Type: research

Bruton ’s tyrosine kinase: an emerging targeted therapy in myeloid cells within the tumor microenvironment
AbstractBruton ’s tyrosine kinase (BTK) is a non-receptor kinase belonging to the Tec family of kinases. The role of BTK in B cell receptor signaling is well defined and is known to play a key role in the proliferation and survival of malignant B cells. Moreover, BTK has been found to be expressed in cells of th e myeloid lineage. BTK has been shown to contribute to a variety of cellular pathways in myeloid cells including signaling in the NLRP3 inflammasome, receptor activation of nuclear factor-κβ and inflammation, chemokine receptor activation affecting migration, and phagocytosis. Myeloid cells are cr ...
Source: Cancer Immunology, Immunotherapy - April 5, 2021 Category: Cancer & Oncology Source Type: research

Comparison of HBV reactivation between patients with high HBV-DNA and low HBV-DNA loads undergoing PD-1 inhibitor and concurrent antiviral prophylaxis
ConclusionWith concurrent antiviral prophylaxis, HBV-DNA load higher than 500  IU/ml should not be a contraindication for PD-1 inhibitor. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 3, 2021 Category: Cancer & Oncology Source Type: research

Correlation between melatonin concentration and cytokines in cervical mucus in positive samples for the presence of human papillomavirus
This study aimed to quantify and correlate cytokines IL-6, IL-8, and IL-10 and Melatonin in cervical mucus. According to the results, a decrease in MLT was observed in LSIL, HSI, and ASC-H groups than in the NILM group. The cytokines IL-6 and IL-8 showed greater expression in the LSIL and HSIL groups than the NILM group. HSIL group showed a negative correlation between the MLT and IL-6 and IL-8 concentrations. In the ASC-US group, IL8 level was positively correlated to MLT levels. We suggest that IL-6, IL-8, and MLT levels in HSIL groups are decisive for the progression of neoplastic lesions in HPV infections. New cervical...
Source: Cancer Immunology, Immunotherapy - April 2, 2021 Category: Cancer & Oncology Source Type: research

Myeloid cell heterogeneity in lung cancer: implication for immunotherapy
AbstractLung is a specialized tissue where metastases from primary lung tumors takeoff and those originating  from extra-pulmonary sites land. One commonality characterizing these processes is the supportive role exerted by myeloid cells, particularly neutrophils, whose recruitment is facilitated in this tissue microenvironment. Indeed, neutrophils have important part in the pathophysiology of this organ and the key mechanisms regulating neutrophil expansion and recruitment during infection can be co-opted by tumor cells to promote growth and metastasis. Although neutrophils dominate the myeloid landscape of lung...
Source: Cancer Immunology, Immunotherapy - April 2, 2021 Category: Cancer & Oncology Source Type: research

Cancer therapy in mice using a pure population of CD8 +  T cell specific to the AH1 tumor rejection antigen
AbstractThere is a growing interest in the use of patient-derived T cells for the treatment of various types of malignancies. The expansion of a polyclonal and polyspecific population of tumor-reactive T cells, with a subsequent infusion into the same donor patient, has been implemented, sometimes with positive results. It is not known, however, whether a set of T cells with a single antigen specificity may be sufficient for an effective therapy. To gain more insights in this matter, we used naturally occurring T cells recognizing a retroviral peptide (AH1), which is endogenous in many tumor cell lines of BALB/c origin and...
Source: Cancer Immunology, Immunotherapy - April 1, 2021 Category: Cancer & Oncology Source Type: research

Assessment of systematic inflammatory and nutritional indexes in extensive-stage small-cell lung cancer treated with first-line chemotherapy and atezolizumab
ConclusionPre-treatment PLR could serve as a valuable independent prognostic factor for ES-SCLC who receive chemotherapy and immune checkpoint inhibitors. Further, prospective studies are still needed to confirm our findings. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 1, 2021 Category: Cancer & Oncology Source Type: research

Reduction of derived neutrophil-to-lymphocyte ratio after four weeks predicts the outcome of patients receiving second-line chemotherapy for metastatic colorectal cancer
AbstractSystemic inflammation response (SIR) plays a role in predicting prognosis of patients with metastatic colorectal cancer (mCRC). Chemotherapy-induced neutropenia has been suggested as another evaluable prognostic and predictive factor. This is a retrospective analysis of derived neutrophil-to-lymphocyte ratio (dNLR) and its reduction  >  10% after the first cycle of chemotherapy (R10) in a monoinstitutional series of patients with mCRC receiving a first-line and a second-line cytotoxic chemotherapy. The effects of the neutrophil-related variables on overall survival (OS) and on chemotherapy activity...
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

Improvement of DC-based vaccines using adjuvant TLR4-binding 60S acidic ribosomal protein P2 and immune checkpoint inhibitors
In this study, we identified 60S acidic ribosomal protein P2 (RPLP2) through pull-down assay using human cancer cells derived proteins that binds to Toll-like receptor 4 (TLR4). Recombinant RPLP2 induced maturation and activation of DCs in vitro. This DC-based vaccine, followed by pulsing with tumor-specific antigen, has shown to significantly increase tumor-specific CD8+IFN- γ+ T cells, and improved both tumor prevention and tumor treatment effects in vivo. The adjuvant effects of RPLP2 were shown to be dependent on TLR4 using TLR4 knockout mice. Moreover, ICIs that suppress the tumor evasion mechanism showed synerg...
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

PD-1 blockade synergizes with intratumoral vaccination of a therapeutic HPV protein vaccine and elicits regression of tumor in a preclinical model
ConclusionsOur results provide rationale for future clinical testing of intratumoral TA-CIN vaccination in combination with PD-1 blockade for the control of HPV16-associated tumors. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

Tuberculosis following programmed cell death receptor-1 (PD-1) inhibitor in a patient with non-small cell lung cancer. Case report and literature review
AbstractImmune checkpoint inhibitors (ICIs) —anti-programmed death-1 (PD-1) and their ligands (PD-L1 and PD-L2) have become widely used in the treatment of several malignancies. Many immune-related adverse events (irAEs) have been linked to these agents. Nonetheless, tuberculosis (TB) reactivation during their use is increasingly recognized and reported. Herein, we present a 58-year-old lady with advanced non-small cell lung cancer (NSCLC) ALK-negative, EGFR wild, and PD-L1 immune histochemistry (IHC) strongly positive in 95% of tumor cells, on ongoing treatment with Pembrolizumab as a first-line monotherapy. Our pat...
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

Merkel cell carcinoma in Latin America: a contribution from an expanded access program for avelumab to address issues from experts ’ recommendations
ConclusionAvelumab showed robust efficacy and a safety profile consistent with global EAP data. Results are aimed to improve current knowledge about mMCC treatment and access to immunooncologic strategies for treating LATAM patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

Prognostic role of gamma-glutamyl transferase in metastatic melanoma patients treated with immune checkpoint inhibitors
ConclusionsThe frequency of hepatic irAE is currently underestimated. The addition of the sensitive enzyme GGT to the laboratory panel before and during therapy with ICPI allows to detect two to three times more patients developing hepatic or hepatobiliary toxicity than known so far. Immune-related GGT elevations correlate with response and favorable survival.Precis for use in the Table of ContentsThe frequency of hepatotoxicity under immune checkpoint blockade is currently underestimated. We suggest the addition of gamma-glutamyl transferase to the laboratory panel in checkpoint inhibitor patients for the detection of hep...
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

Notch signaling defects in NK cells in patients with cancer
AbstractAltered expressions of proto-oncogenes have been reported during normal lymphocytes mitogenesis and in T and B lymphocytes in patients with autoimmune diseases. We have recently demonstrated a significantly decreased expression of c-kit and c-Myc in NK cells isolated from patients with cancer, which might be related to the functional deficiency of NK cells in the tumor environment. Here, focusing on the regulatory mechanisms of this new clinical phenomenon, we determined expression of c-Myc, Notch1, Notch2, p-53, Cdk6, Rb and phosphorylated Rb in NK cells isolated from the healthy donors and cancer patients. The re...
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

Retinoblastoma cell-derived Twist protein promotes regulatory T cell development
ConclusionsRbcs express Twist, that induces IL-4+ Foxp3+ Tregs; the latter can inhibit CD8+ cytotoxic T cell activities. Therefore, Twist may play an important role in the pathogenesis of Rb. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

Novel adjuvant dendritic cell therapy with transfection of heat-shock protein 70 messenger RNA for patients with hepatocellular carcinoma: a phase I/II prospective randomized controlled clinical trial
ConclusionThe HSP70 mRNA-transfected DC therapy was performed safely as an adjuvant therapy. The prognosis of HSP70-expressing HCC cases could be expected to improve with this therapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

Response to radiotherapy in pancreatic ductal adenocarcinoma is enhanced by inhibition of myeloid-derived suppressor cells using STAT3 anti-sense oligonucleotide
In this study, we analyze changes in immune cell populations and circulating chemokines in patient samples and animal models of pancreatic cancer to characterize the immune response to radiotherapy. Further, we identify STAT3 as a key mediator of immunosuppression post-RT. We found granulocytic MDSCs (G-MDSCs) and neutrophils to be increased in response to RT in murine and human PDAC samples. We also found that RT-induced STAT3 phosphorylation correlated with increased MDSC infiltration and proliferation. Targeting STAT3 using an anti-sense oligonucleotide in combination with RT circumvented RT-induced MDSC infiltration, e...
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway
ConclusionOSCC cell-secreted exosomalCMTM6 induces M2-like macrophages polarization to promote malignant progression via ERK1/2 signaling pathway, revealing a novel crosstalk between cancer cells and immune cells in OSCC microenvironment. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

Overcoming acquired resistance to PD-1 inhibitor with the addition of metformin in small cell lung cancer (SCLC)
AbstractMetformin has been widely used as the treatment of type II diabetes mellitus for its anti-hyperglycemic effect. In recent years, it has also been extensively studied for its anti-cancer effect as it diminishes immune exhaustion of CD8  + tumor-infiltrating lymphocytes (TILs). It decreases apoptosis of CD8 + TILs, thereby enhancing T cell-mediated immune response to tumor cells. Here, we present a unique case of a patient with small cell lung cancer (SCLC) who exhibited an overall partial response as per Response Evaluatio n Criteria in Solid Tumors, version 1.1 (RECIST 1.1) since startin...
Source: Cancer Immunology, Immunotherapy - March 20, 2021 Category: Cancer & Oncology Source Type: research

The impact of selenium on regulatory T cell frequency and immune checkpoint receptor expression in patients with  diffuse large B cell lymphoma (DLBCL)
AbstractFor many decades, selenium (Se) has been known as a potential anti-cancer agent that can also improve the function of immune cells in a variety of solid tumors. However, there is no report on the role of Se on CD4+ T cell subsets like CD4+CD25+FOXP3+ regulatory T cells (Tregs) in lymphoma patients. In this randomized clinical trial, we investigated the effect of 3-month Se consumption on the frequency of CD4+CD25+FOXP3+ Tregs and the expression of immune checkpoint receptors in thirty-two non-Hodgkin lymphoma (NHL) patients (16 patients with Se (Se+) and 16 without Se (Se −) consumption) with diffuse large B-...
Source: Cancer Immunology, Immunotherapy - March 15, 2021 Category: Cancer & Oncology Source Type: research

Tumor immune microenvironment in brain metastases from gynecologic malignancies
ConclusionAn active tumor immune microenvironment is present with similar distribution in the primary disease site and BM from patients with gynecologic malignancies. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 13, 2021 Category: Cancer & Oncology Source Type: research

Polymorphism of formyl peptide receptor 1 (FPR1) reduces the therapeutic efficiency and antitumor immunity after neoadjuvant chemoradiotherapy (CCRT) treatment in locally advanced rectal cancer
In this study, we investigated several genotypes of pattern recognition receptors (PRRs) and their impact on therapeutic efficacy in LARC patients treated with CCRT. We found that homozygosis of formyl peptide receptor 1 (FPR1) (E346A/rs867228) was associated with reduced 5-year overall survival (OS) by Kaplan –Meier analysis (62% vs. 81%,p = 0.014) and multivariate analysis [hazard ratio (HR) = 3.383, 95% CI = 1.374–10.239,p = 0.007]. Moreover, in an animal model, we discovered that the FPR1 antagonist, Boc-MLF (Boc-1), reduced CCRT therapeutic efficacy a...
Source: Cancer Immunology, Immunotherapy - March 13, 2021 Category: Cancer & Oncology Source Type: research

Combining UBR5 and CD163 + tumor-associated macrophages better predicts prognosis of clear cell renal cell carcinoma patients
ConclusionsIntegrating intratumoral UBR5 and CD163+ TAMs with the current clinical parameters achieves better accuracy in predicting ccRCC patients ’ postoperative prognosis. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 12, 2021 Category: Cancer & Oncology Source Type: research

Correction to: Transcriptome of CD8 + tumor-infiltrating T cells: a link between diabetes and colorectal cancer
A correction to this paper has been published: https://doi.org/10.1007/s00262-021-02903-w (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 12, 2021 Category: Cancer & Oncology Source Type: research

Natural killer cells efficiently target multiple myeloma clonogenic tumor cells
AbstractThe multiple myeloma (MM) landscape has changed in the last few years, but most patients eventually relapse because current treatment modalities do not target clonogenic stem cells, which are drug-resistant and can self-renew. We hypothesized that side population (SP) cells represent myeloma clonogenic stem cells and, searching for new treatment strategies, analyzed the anti-myeloma activity of natural killer (NK) cells against clonogenic cells. Activated and expanded NK cells (NKAE) products were obtained by co-culturing NK cells from MM patients with K562-mb15-41BBL cell line and characterized by flow cytometry. ...
Source: Cancer Immunology, Immunotherapy - March 10, 2021 Category: Cancer & Oncology Source Type: research

The clinical implication of soluble PD-L1 (sPD-L1) in patients with breast cancer and its biological function in regulating the function of T lymphocyte
AbstractThis work investigated the clinical prognostic implications and biological function of plasma soluble programmed cell death ligand 1 in breast cancer patients. Plasma sPD-L1 levels of recurrent/metastatic breast cancer patients were determined, and the association of sPD-L1 levels and metastatic progression-free survival and metastatic overall survival was assessed. The PD-L1 expression on breast cancer cells was analyzed by flow cytometry, and the level of sPD-L1 in the supernatant of breast cancer cells was determined by enzyme-linked immunosorbent assay. Furthermore, the effect of sPD-L1 on the proliferation and...
Source: Cancer Immunology, Immunotherapy - March 10, 2021 Category: Cancer & Oncology Source Type: research

Clinical significance of peripheral TCR and BCR repertoire diversity in EGFR/ALK wild-type NSCLC treated with anti-PD-1 antibody
ConclusionsThese findings suggest the clinical significance of changes in peripheral TCR and BCR repertoire diversity after anti-PD-1 treatment in patients with NSCLC without EGFR/ALK mutation. Monitoring of the peripheral TCR and BCR repertoires may serve as a surrogate marker for the early detection of EGFR/ALK wild-type NSCLC patients who would benefit from anti-PD-1 treatment. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 9, 2021 Category: Cancer & Oncology Source Type: research

Correction to: CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma
The original version of this article unfortunately contained a mistake. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 9, 2021 Category: Cancer & Oncology Source Type: research

Effect of chemoradiotherapy on the proportion of circulating lymphocyte subsets in patients with limited-stage small cell lung cancer
ConclusionsCRT induced changes in the proportion of circulating lymphocyte subsets in LS-SCLC, which is helpful for designing a regimen of immune drugs to be combined with CRT. The prognostic value of the proportion of lymphocytes aids in understanding the role of peripheral immune profiles in LS-SCLC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 6, 2021 Category: Cancer & Oncology Source Type: research

Boosting CAR T-cell responses in lymphoma by simultaneous targeting of CD40/4-1BB using oncolytic viral gene therapy
In conclusion, immunostimulatory LOAd703 therapy is an intriguing approach to induce anti-lymphoma immune responses and to improve CAR T-cell therapy in B-cell lymphoma. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 5, 2021 Category: Cancer & Oncology Source Type: research

Identified lung adenocarcinoma metabolic phenotypes and their association with tumor immune microenvironment
ConclusionsThis work revealed the significant connection between metabolic pattern of tumor and tumor immune infiltration, regulating LUAD patients ’ response to immunotherapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - March 3, 2021 Category: Cancer & Oncology Source Type: research

Potentially functional variants of ERAP1, PSMF1 and NCF2 in the MHC-I-related pathway predict non-small cell lung cancer survival
AbstractBackgroundCellular immunity against tumor cells is highly dependent on antigen presentation by major histocompatibility complex class I (MHC-I) molecules. However, few published studies have investigated associations between functional variants of MHC-I-related genes and clinical outcomes of lung cancer patients.MethodsWe performed a two-phase Cox proportional hazards regression analysis by using two previously published genome-wide association studies to evaluate associations between genetic variants in the MHC-I-related gene set and the survival of non-small cell lung cancer (NSCLC) patients, followed by expressi...
Source: Cancer Immunology, Immunotherapy - March 2, 2021 Category: Cancer & Oncology Source Type: research