Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%
The objective response rate (ORR) was 44.5% (95% CI 40.2 –49.1), while the median progression free survival (PFS) and overall survival (OS) were 7.9 months (95% CI 6.9–9.5; 599 events) and 17.2 months (95% CI 15.3–22.3; 598 censored patients), respectively. ECOG-PS ≥ 2 (p 
Source: Cancer Immunology, Immunotherapy - October 17, 2020 Category: Cancer & Oncology Source Type: research

Brief report: inhaled corticosteroid use and the risk of checkpoint inhibitor pneumonitis in patients with advanced cancer
AbstractBackgroundCheckpoint inhibitor pneumonitis (CIP) is an immune-related adverse event that may complicate treatment with immune checkpoint inhibitors (ICI) and can cause significant morbidity. We sought to identify predictors for the development of CIP, and whether the use of inhaled corticosteroids (ICS) at time of ICI may be protective.MethodsPatients with advanced cancer treated with ICI from 2011 and 2018 were included in this study. CIP attribution to ICI was determined by treating physician at time of diagnosis. Predictors were assessed by univariate and multivariable Cox proportional hazard models.ResultsWe id...
Source: Cancer Immunology, Immunotherapy - October 17, 2020 Category: Cancer & Oncology Source Type: research

In vitro 4-1BB stimulation promotes expansion of CD8 + tumor-infiltrating lymphocytes from various sarcoma subtypes
In conclusion, TIL expansion from sarcoma is feasible and expanded TILs highly express LAG3 and comprise multifunctional tumor-reactive T-cells. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 17, 2020 Category: Cancer & Oncology Source Type: research

Differences in PD-1 expression on CD8+ T-cells in chronic myeloid leukemia patients according to disease phase and TKI medication
In this study, we evaluated the expression of an immune checkpoint programmed death 1 (PD-1) on T-cell subsets in chronic myeloid leukemia (CML). We obtained bone marrow aspirate samples from CML patients and from individuals without evidence of hematologic malignancies (controls). PD-1 expression on T-cell subsets was measured using flow cytometric analysis. PD-1 expression levels on CD8+ T-cells were significantly lower in complete hematologic response (CHR) than in controls, chronic phase, and blast phase (BP). In CML patients receiving imatinib and dasatinib, PD-1 expression levels on CD8+ T-cells were lower than that ...
Source: Cancer Immunology, Immunotherapy - October 17, 2020 Category: Cancer & Oncology Source Type: research

Augmenting engineered T-cell strategies in solid cancers through epigenetic priming
AbstractT-cell receptor (TCR)- and chimeric antigen receptor (CAR)-based adoptive cell transfer (ACT) has shown promising results in hematological malignancies, but remains immature in solid cancers. The challenges associated with identification of tumor-specific targets, the heterogenic antigen expression, limited T-cell trafficking to tumor sites and the hostile tumor microenvironment (TME), are all factors contributing to the limited efficacy of ACT therapies against solid tumors. Epigenetic priming of tumor cells and the microenvironment may be a way of overcoming these obstacles and improving the clinical efficacy of ...
Source: Cancer Immunology, Immunotherapy - October 17, 2020 Category: Cancer & Oncology Source Type: research

Differences in the sensitivity of classically and alternatively activated macrophages to TAK1 inhibitor-induced necroptosis
AbstractControlling the balance of pro-inflammatory M1 versus anti-inflammatory M2 macrophages may have paramount therapeutic benefit in cardiovascular diseases, infections, cancer and chronic inflammation. The targeted depletion of different macrophage populations provides a therapeutic option to regulate macrophage-mediated functions. Macrophages are highly sensitive to necroptosis, a newly described regulated cell death mediated by receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain like pseudokinase. Antagonists of inhibitors of apoptosis proteins (SMAC mimetics) block ...
Source: Cancer Immunology, Immunotherapy - October 17, 2020 Category: Cancer & Oncology Source Type: research

A pan-cancer analysis of the human tumor coagulome and its link to the tumor immune microenvironment
ConclusionThese tumor-specific patterns of expression might partially explain the differences in VTE risk among tumor types.  We propose that biomarkers of coagulation fibrinolysis might provide valuable information about the TME in cancer patients. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 15, 2020 Category: Cancer & Oncology Source Type: research

Patients with gastrointestinal irritability after TGN1412-induced cytokine storm displayed selective expansion of gut-homing αβ and γδT cells
AbstractFollowing infusion of the anti-CD28 superagonist monoclonal antibody TGN1412, three of six previously healthy, young male recipients developed gastrointestinal irritability associated with increased expression of ‘gut-homing’ integrin β7 on peripheral blood αβT cells. This subset of patients with intestinal symptoms also displayed a striking and persistent expansion of putative Vδ2+γδT cells in the circulation which declined over a 2-year period following drug infusion, concordant with subsiding gut symptoms. These data demonstrate that TGN1412-induced gastrointestinal ...
Source: Cancer Immunology, Immunotherapy - October 13, 2020 Category: Cancer & Oncology Source Type: research

Sustained IL-2R signaling of limited duration by high-dose mIL-2/mCD25 fusion protein amplifies tumor-reactive CD8 + T cells to enhance antitumor immunity
In this study, we modeled an alternative strategy to amplify tumor antigen-specific TCR transgenic CD8+ T cells through limited application of a long-acting IL-2 fusion protein, mIL-2/mCD25, which selectively targets the high-affinity IL-2R. Here, mice were vaccinated with a tumor antigen and high-dose mIL-2/mCD25 was applied to coincide with the induction of the high affinity IL-2R on tumor-specific T cells. A single high dose of mIL-2/mCD25, but not an equivalent amount of IL-2, amplified the frequency and function of tumor-reactive CD8+ T effector (Teff) and memory cells. These mIL-2/mCD25-dependent effects relied on di...
Source: Cancer Immunology, Immunotherapy - October 10, 2020 Category: Cancer & Oncology Source Type: research

Combination therapies utilizing neoepitope-targeted vaccines
AbstractClinical successes have been achieved with checkpoint blockade therapy, which facilitates the function of T cells recognizing tumor-specific mutations known as neoepitopes. It is a reasonable hypothesis that therapeutic cancer vaccines targeting neoepitopes uniquely expressed by a patient ’s tumor would prove to be an effective therapeutic strategy. With the advent of high-throughput next generation sequencing, it is now possible to rapidly identify these tumor-specific mutations and produce therapeutic vaccines targeting these patient-specific neoepitopes. However, initial reports suggest that when used as a...
Source: Cancer Immunology, Immunotherapy - October 8, 2020 Category: Cancer & Oncology Source Type: research

Immune reconstitution and clinical recovery following anti-CD28 antibody (TGN1412)-induced cytokine storm
AbstractCytokine storm can result from cancer immunotherapy or certain infections, including COVID-19. Though short-term immune-related adverse events are routinely described, longer-term immune consequences and sequential immune monitoring are not as well defined. In 2006, six healthy volunteers received TGN1412, a CD28 superagonist antibody, in a first-in-man clinical trial and suffered from cytokine storm. After the initial cytokine release, antibody effect-specific immune monitoring started on Day  + 10 and consisted mainly of evaluation of dendritic cell and T-cell subsets and 15 serum cytokines at 21 ti...
Source: Cancer Immunology, Immunotherapy - October 8, 2020 Category: Cancer & Oncology Source Type: research

Chimeric antigen receptor (CAR)-T-cell therapy in non-small-cell lung cancer (NSCLC): current status and future perspectives
AbstractThere has been a rapid progress in developing genetically engineered T cells in recent years both in basic and clinical cancer studies. Chimeric antigen receptor (CAR)-T cells exert an immune response against various cancers, including the non-small-cell lung cancer (NSCLC). As novel agents of immunotherapy, CAR-T cells show great promise for NSCLC. However, targeting specific antigens in NSCLC with engineered CAR-T cells is complicated because of a lack of tumor-specific antigens, the immunosuppressive tumor microenvironment, low levels of infiltration of CAR-T cells into tumor tissue, and tumor antigen escape. Me...
Source: Cancer Immunology, Immunotherapy - October 5, 2020 Category: Cancer & Oncology Source Type: research

Pembrolizumab and atezolizumab in triple-negative breast cancer
AbstractTriple-negative breast cancer (TNBC) is defined by a lack of expression of both estrogen (ER) and progesterone (PgR) receptors as well as human epidermal growth factor receptor 2 (HER2) and is associated with poor prognosis. Moreover, the systemic treatment options are limited. However, the TNBC is more likely than other breast cancer subtypes to benefit from immune checkpoint blockade therapy due to its higher immunogenicity, higher enrichment by tumour-infiltrating lymphocytes (TILs), and higher levels of programmed cell death ligand 1 (PD-L1) expression. Thus far, atezolizumab was approved in combination with na...
Source: Cancer Immunology, Immunotherapy - October 4, 2020 Category: Cancer & Oncology Source Type: research

Immune resilience in response to cancer therapy
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 3, 2020 Category: Cancer & Oncology Source Type: research

Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma
AbstractThermal ablative therapies are standard treatments for localized hepatocellular carcinoma (HCC). In addition to local tumor destruction, ablation leads to abscopal effects in distant lesions most likely mediated by an anti-tumor immune response. Although microwave ablation (MWA) is increasingly substituting other ablative techniques, its systemic immunostimulatory effects are poorly studied. We analyzed tumor-specific immune responses in peripheral blood of HCC patients after thermal ablation with regard to T cell responses and disease outcome. While comprehensive flow cytometric analyses in sequential samples of a...
Source: Cancer Immunology, Immunotherapy - October 1, 2020 Category: Cancer & Oncology Source Type: research

PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck squamous cell carcinomas
ConclusionsHigh infiltration by CD8+ TIL is associated with better survival outcomes. Positive PD-L1 expression correlates with a high infiltration by TILs, explaining its association with better prognosis. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

Immune checkpoint inhibitors reverse tolerogenic mechanisms induced by melanoma targeted radionuclide therapy
AbstractIn line with the ongoing phase I trial (NCT03784625) dedicated to melanoma targeted radionuclide therapy (TRT), we explore the interplay between immune system and the melanin ligand [131I]ICF01012 alone or combined with immunotherapy (immune checkpoint inhibitors, ICI) in preclinical models. Here we demonstrate that [131I]ICF01012 induces immunogenic cell death, characterized by a significant increase in cell surface-exposed annexin A1 and calreticulin. Additionally, [131I]ICF01012 increases survival in immunocompetent mice, compared to immunocompromised (29 vs. 24  days,p = 0.0374). Flow cytomet...
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

NKG2D-Fc fusion protein promotes antitumor immunity through the depletion of immunosuppressive cells
In conclusion, NKG2D-Fc induces antitumor immunity and tumor control through the depletion of MDSCs and Tregs, subsequently providing a niche for the infiltration and expansion of proinflammatory cells, such as NK cells. Strategies capable of modulating the immunosuppressive state in cancer are in high clinical demand. NK G2D-Fc is a simple, single tool capable of depleting both MDSCs and Tregs and should be further investigated as a therapeutic agent for the treatment of cancer. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

Development of CDX-527: a bispecific antibody combining PD-1 blockade and CD27 costimulation for cancer immunotherapy
AbstractCD27 is a costimulatory molecule that provides a complementary target to the PD-1/PD-L1 checkpoint axis on T cells. Combining a CD27 agonist antibody with PD-1/PD-L1 blockade has shown synergistic antitumor activity in preclinical models, which led to clinical studies of the combination in cancer patients. We theorized that coupling CD27 costimulation with PD-1/PD-L1 blockade in a bispecific antibody (BsAb) may provide greater immune activating properties than combining the individual mAbs due to enhanced CD27 activation by cross-linking through PD-L1 and Fc receptors. To test this approach, we developed CDX-527, a...
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

Economic evaluations of cancer immunotherapy: a systematic review and quality evaluation
ConclusionsWhether or not these findings will be confirmed remains to be seen when market approval to cover more indications is extended and new effective immunotherapeutic agents become available. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

Galectin-9 expression as a poor prognostic factor in patients with renal cell carcinoma
AbstractRecently, the effectiveness of anti-programmed death 1 (PD-1) antibody therapy in the treatment of renal cell carcinoma (RCC) has been established. Nevertheless, efficacy has been reported to be limited to only 10 –30% of patients. To develop more effective immunotherapy for RCC, we analyzed the immunological characteristics in RCC tissues by immunohistochemistry (IHC). We prepared a tissue microarray that consisted of tumor tissue sections (1 mm in diameter) from 83 RCC patients in Kanagawa Cancer Center between 2006 and 2015. IHC analysis was performed with antibodies specific to immune-related (C...
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

Primary breast tumours but not lung metastases induce protective anti-tumour immune responses after Treg-depletion
This study examined the impact of depleting Foxp3+ regulatory T cells (Treg), on lung metastases, using a mouse model of breast cancer. After Treg-depletion, generation of an immune response to the primary tumour was a critical determinant for limiting development of metastasis. Indeed, resection of the primary tumour abrogated any effect of Treg-depletion on metastases. In addition, whilst the immune response, generated by the primary tumour, prevented metastases development, it had little impact on controlling established disease. Collectively, the data indicate that metastatic cells in the lung are not controlled by imm...
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

Sex differences in the association between tumor growth and T cell response in a melanoma mouse model
AbstractEpidemiological evidence suggests that females have an advantage over males in cases of melanoma incidence, progression, and survival. However, the biological mechanisms underlying these sex differences remain unclear. With the knowledge that females generally have a more robust immune system than males, we investigated sex differences in melanoma progression in a B16-F10/BL6 syngeneic mouse model. We observed significantly less tumor volume and growth rate over 14  days in female mice compared to male mice. Furthermore, higher populations of CD4+ and CD8+ T cells, which indicate adaptive immune responses, wer...
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

Systemic but not MDSC-specific IRF4 deficiency promotes an immunosuppressed tumor microenvironment in a murine pancreatic cancer model
This study demonstrates a critical role of IRF4 in the generation of an immunosuppressive tumor microenvironment in pancreatic cancer, which is independent of IRF4 expression in PMN-MDSC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

Antitumor efficacy of BAFF-R targeting CAR T cells manufactured under clinic-ready conditions
AbstractB-cell malignancies can potentially be cured by CD19 chimeric antigen receptor (CAR) T-cell therapy. Although clinical response rates can be up to 93% in acute lymphoblastic leukemia, treatment-related antigen loss and lack of therapeutic persistence contribute to disease relapse. These shortcomings of current CAR T-cell therapy indicate the need for biologically relevant target selection and for improving the efficacy and persistence of the CAR T cells, which we have addressed by developing a novel B-cell activating factor receptor (BAFF-R) CAR T-cell therapy with improved therapeutic persistence. BAFF-R is a B-ce...
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

A TLR4 –TRIF-dependent signaling pathway is required for protective natural tumor-reactive IgM production by B1 cells
AbstractMetastatic cancer involving spread to the peritoneal cavity is referred to as peritoneal carcinomatosis and has a very poor prognosis. Our previous studies demonstrated a toll-like receptor 4 (TLR4) and C-type lectin receptor (CLR; Mincle/MCL) agonist pairing of monophosphoryl lipid A (MPL) and trehalose-6,6 ′-dicorynomycolate (TDCM) effectively inhibits peritoneal tumor growth and ascites development through a mechanism dependent upon B1a cell-produced natural IgM, complement, and phagocytes. In the current study, we investigated the requirement for TLR4 and Fc receptor common γ chain (FcRγ), req...
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

Are we ready to use TMB in breast cancer clinical practice?
AbstractWe discussed the potentialities of tumor mutation burden (TMB) as a predictive marker for immunotherapy in breast cancer, also highlighting the limits that have hindered its introduction in the clinical practice. Although some studies have demonstrated the possibility to select patients more responsive to immune-checkpoint inhibitors by evaluating TMB, some issues emerged regarding the complexity of the methodologies for its determination, the costs of the analysis, and the necessity to improve the TMB determination with that of neoantigen identification. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 23, 2020 Category: Cancer & Oncology Source Type: research

Silent acute appendicitis revealed by PET-CT during treatment with ipilimumab and nivolumab: a new immune-related adverse event
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 21, 2020 Category: Cancer & Oncology Source Type: research

Flow cytometric analysis of  circulating endothelial cells and endothelial progenitor cells in pediatric solid tumors: prognostic impact on treatment response and survival
AbstractBackground and aimSolid tumors, including pediatric malignancies, depend on angiogenesis for tumor growth, invasion, and metastases. We aimed to evaluate the prognostic impact of circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) on treatment response and survival of pediatric patients with solid tumors.MethodsA prospective study included 70 patients with different pediatric solid tumors treated with different types of chemotherapy and 20 age and sex-matched healthy children as controls. Blood samples collected at diagnosis then on day 7 and day 21 after chemotherapy. CECs and EPCs were ev...
Source: Cancer Immunology, Immunotherapy - September 17, 2020 Category: Cancer & Oncology Source Type: research

Hyperprogressive disease rarely occurs during checkpoint inhibitor treatment for advanced melanoma
ConclusionHyperprogression is rare in melanoma patients treated with immune checkpoint inhibitors. Our data question if hyperprogression really is a biological entity in metastatic melanoma. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 13, 2020 Category: Cancer & Oncology Source Type: research

Reviving up dendritic cells can run cancer immune wheel in non-small cell lung cancer: a prospective two-arm study
This study was a case-controlled one, included 50 patients with denovo pathologically confirmed NSCLC and 20 healthy controls of comparable age and gender. After diagnosis and staging of patients, the frequency of DCs was evaluated using flow cytometry.ResultsWe unveiled significantly reduced levels of pDCs (P = 0.024), and mDCs (P = 0.013) in NSCLC patients compared to controls. Furthermore, there was a significant accumulation of pDCs in non-metastatic patients compared to metastatic ones (P 
Source: Cancer Immunology, Immunotherapy - September 11, 2020 Category: Cancer & Oncology Source Type: research

A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC)
ConclusionsAMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 11, 2020 Category: Cancer & Oncology Source Type: research

A systematic scoping review on natural killer cell function in colorectal cancer
ConclusionsNK cell morphology and function are significantly affected by the development of colorectal cancer. Observation of NK cell changes may lead to earlier detection and better prognostication in colorectal cancer. Further study is needed into immunological manipulation of NK cells which may lead to improved colorectal cancer survival. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 10, 2020 Category: Cancer & Oncology Source Type: research

Toxicity with small molecule and immunotherapy combinations in non-small cell lung cancer
AbstractTreatment stratification in stage IV NSCLC is guided by identification of oncogene driver mutations. Actionable mutations with current licenced therapeutic agents include epidermal growth factor receptor (EGFR), rearrangements of anaplastic lymphoma kinase (ALK), ROS-1 and BRAF V600. Alongside progress with small molecule therapy, developments in immune checkpoint inhibitors (CPIs) have transformed the landscape of stage III and stage IV NSCLC. The success of CPIs has led to evaluation with small molecule therapy in both concurrent and sequential settings. In this review we summarise recent results of combination C...
Source: Cancer Immunology, Immunotherapy - September 10, 2020 Category: Cancer & Oncology Source Type: research

Next-generation humanized patient-derived xenograft mouse model for pre-clinical antibody studies in neuroblastoma
AbstractFaithful tumor mouse models are fundamental research tools to advance the field of immuno-oncology (IO). This is particularly relevant in diseases with low incidence, as in the case of pediatric malignancies, that rely on pre-clinical therapeutic development. However, conventional syngeneic and genetically engineered mouse models fail to recapitulate the tumor heterogeneity and microenvironmental complexity of human pathology that are essential determinants of cancer-directed immunity. Here, we characterize a novel mouse model that supports human natural killer (NK) cell development and engraftment of neuroblastoma...
Source: Cancer Immunology, Immunotherapy - September 10, 2020 Category: Cancer & Oncology Source Type: research

Post-treatment neutrophil-to-lymphocyte ratio (NLR) predicts response to anti-PD-1/PD-L1 antibody in SCLC patients at early phase
AbstractNeutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) have been identified as predictors of treatment response in a variety of cancers. We conducted a retrospective analysis to investigate the usefulness of NLR, PLR and SII at baseline and at 6  weeks post-treatment as predictors of response to anti-PD-1/PD-L1 antibody treatment in small cell lung cancer (SCLC). Data of 41 SCLC patients receiving immunotherapy as second- or later-line treatment were analyzed. The overall median progression-free survival (PFS) was 5.1 months (95% CI 3.2– 6....
Source: Cancer Immunology, Immunotherapy - September 9, 2020 Category: Cancer & Oncology Source Type: research

Immune checkpoint-related serum proteins and genetic variants predict outcomes of localized prostate cancer, a cohort study
AbstractBackgroundThe clinical predictors and biological mechanisms for localized prostate cancer (PCa) outcomes remain mostly unknown. We aim to evaluate the role of serum immune-checkpoint-related (ICK) proteins and genetic variations in predicting outcomes of localized PCa.MethodsWe profiled the serum levels of 14 ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, 4-1BB, CD27, and CTLA-4) in 190 patients with localized PCa. The genotypes of 97 single nucleotide polymorphisms (SNPs) from 19 ICK-related genes were analyzed in an extended population (N = 1762). Meta-dat...
Source: Cancer Immunology, Immunotherapy - September 8, 2020 Category: Cancer & Oncology Source Type: research

Monophosphoryl lipid A-induced activation of plasmacytoid dendritic cells enhances the anti-cancer effects of anti-PD-L1 antibodies
In this study, we explored how MPLA enhanced the anti-cancer effects of anti-PD-L1 antibodies (Abs). Anti-cancer immunity induced by the combination of anti-PD-L1 Abs and MPLA failed in CD4 and CD8 cell-depleted mice. Moreover, the combination treatment of anti-PD-L1 Abs and MPLA synergistically enhanced the activation of plasmacytoid dendritic cells (pDCs) in the mouse in vivo, while conventional DCs were not. In addition, mice treated with anti-PD-L1 Abs and MPLA were not protected from B16 melanoma by blockade of interferon-alpha receptor (IFNAR). The combination of anti-PD-L1 Abs and MPLA also promoted human peripheral...
Source: Cancer Immunology, Immunotherapy - September 8, 2020 Category: Cancer & Oncology Source Type: research

Varied functions of immune checkpoints during cancer metastasis
AbstractImmune checkpoints comprise diverse receptors and ligands including costimulatory and inhibitory molecules, which play monumental roles in regulating the immune system. Immune checkpoints retain key potentials in maintaining the immune system homeostasis and hindering the malignancy development and autoimmunity. The expression of inhibitory immune checkpoints delineates an increase in a plethora of metastatic tumors and the inhibition of these immune checkpoints can be followed by promising results. On the other hand, the stimulation of costimulatory immune checkpoints can restrain the metastasis originating from d...
Source: Cancer Immunology, Immunotherapy - September 8, 2020 Category: Cancer & Oncology Source Type: research

Increased thyroid uptake on 18F-FDG PET/CT is associated with the development of permanent hypothyroidism in stage IV melanoma patients treated with anti-PD-1 antibodies
ConclusionSUVmax-Th  >  4.1 and Th/B >  2.0 provided perfect diagnostic performances to detect patients that developed PTD. No significant survival difference was found between patients with and without increased thyroid uptake. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 2, 2020 Category: Cancer & Oncology Source Type: research

Unique TP53 neoantigen and the immune microenvironment in long-term survivors of Hepatocellular carcinoma
AbstractNeoantigens are T-cell antigens derived from protein-coding mutations in tumor cells. Although neoantigens have recently been linked to anti-tumor immunity in long-term survivors of cancers such as melanoma, their prognostic and immune-modulatory role in many cancer types remain unexplored. We investigate neoantigens in hepatocellular carcinoma (HCC) through a combination of whole exome sequencing (WES), RNA sequencing (RNA-seq), computational bioinformation, and immunohistochemistry. Our analysis reveals that patients carried withTP53 neoantigen have a longer overall survival than others (p = 0.0371)...
Source: Cancer Immunology, Immunotherapy - September 1, 2020 Category: Cancer & Oncology Source Type: research

Early C-reactive protein kinetics predict survival of patients with advanced urothelial cancer treated with pembrolizumab
AbstractObjectiveTo assess the prognostic and predictive ability of early C-reactive protein (CRP) kinetics, dynamic changes in CRP levels, in patients with advanced urothelial cancer treated with pembrolizumab.Patients and methodsWe retrospectively evaluated 97 patients with advanced urothelial cancer treated with pembrolizumab in second-line or later settings. Patients were divided into three early CRP kinetics groups: non-elevated (baseline CRP  
Source: Cancer Immunology, Immunotherapy - September 1, 2020 Category: Cancer & Oncology Source Type: research

Anti-angiogenesis therapy overcomes the innate resistance to PD-1/PD-L1 blockade in VEGFA-overexpressed mouse tumor models
In this study, we endeavored to assess the tumor microenvironment (TME) in VEGFA-overexpressed human tumors and mouse tumor models, and to explore whether anti-angiogenesis therapy can overcome the innate resistance to ICI in hyperangiogenesis mouse tumor models and the underlying mechanism. Effect of VEGFA on clinical prognosis and TME was analyzed using TCGA data. The VEGFA-overexpressed mouse breast and colon subcutaneous models were established. PD-1 mAb or apatinib alone and combination therapy were used. Immunohistochemistry and immunofluorescence were used to assess angiogenesis and hypoxia. Flow cytometry, RNA sequ...
Source: Cancer Immunology, Immunotherapy - August 13, 2020 Category: Cancer & Oncology Source Type: research

Blockade of CD73 delays glioblastoma growth by modulating the immune environment
This study indicates that CD73 knockdown using a nanotechnological approach to perform nasal delivery of siRNA-CD73 to CNS can potentially regulate the glioblastoma immune microenvironment and delay tumor growth by inducing apoptosis. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 13, 2020 Category: Cancer & Oncology Source Type: research

Peripheral blood markers predictive of outcome and immune-related adverse events in advanced non-small cell lung cancer treated with PD-1 inhibitors
This study explored associations between inflammation-related peripheral blood markers and onset of irAEs and outcome in patients with advanced NSCLC receiving PD-1 inhibitors.MethodsA retrospective analysis was conducted of 102 patients with advanced NSCLC receiving PD-1 inhibitors from January 2017 to May 2019. Cox regression models were employed to assess the prognostic effect of low/high neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and prognostic nutrition index (PNI) on overall survival (OS) and progression-free survival (PFS). Logistic regression models were used to analyze the correlation between ...
Source: Cancer Immunology, Immunotherapy - August 13, 2020 Category: Cancer & Oncology Source Type: research

Rapid noninvasive detection of bladder cancer using survivin antibody-conjugated gold nanoparticles (GNPs) based on localized surface plasmon resonance (LSPR)
ConclusionOur findings showed that using the ELISA technique, the increased level of survivin could be identified in high grades of bladder cancer, but using anti-survivin antibody-conjugated GNPs, bladder cancer can be detected in early stages. The applied method was found to be a rapid tool, dependent on visible color changes and colorimetric detection, without any need for reader devices. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 13, 2020 Category: Cancer & Oncology Source Type: research

Selective targeting of different populations of myeloid-derived suppressor cells by histone deacetylase inhibitors
AbstractMyeloid-derived suppressor cells (MDSCs) are widely implicated in negative regulation of immune responses in cancer. Inhibition of class I histone deacetylases (HDAC) with entinostat has anti-MDSC activity. However, as single agent, it did not delay tumor growth in EL4 and LLC tumor models. Here, we found that entinostat reduced immune suppressive activity of only one type of MDSC —polymorphonuclear, PMN-MDSC, whereas it had no effect on monocytic M-MDSC or macrophages. M-MDSC had high amount of class II HDAC—HDAC6, which was further increased after the treatment of mice with entinostat. Inhibition of H...
Source: Cancer Immunology, Immunotherapy - August 13, 2020 Category: Cancer & Oncology Source Type: research

Impact of corticosteroids on allograft protection in renal transplant patients receiving anti-PD-1 immunotherapy
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 13, 2020 Category: Cancer & Oncology Source Type: research

Systemic therapy for metastatic renal cell carcinoma in the first-line setting: a systematic review and network meta-analysis
ConclusionPembrolizumab plus axitinib seemed to be the most efficacious first-line agents, while nivolumab plus ipilimumab had the most favorable efficacy –tolerability equilibrium. These findings may facilitate individualized treatment strategies and inform future direct comparative trials in an expanding treatment options without direct comparison between approved drugs. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 4, 2020 Category: Cancer & Oncology Source Type: research

Expression pattern, regulation, and clinical significance of TOX in breast cancer
AbstractThymocyte selection-associated high mobility group box protein (TOX) is a transcription factor implicated in the regulation of T cell exhaustion during chronic infection and cancer. While TOX is being targeted for cancer immunotherapy, limited information is available about its significance in breast cancer and other solid tumors. We performed a comprehensive analysis ofTOX gene expression, its epigenetic regulation, protein localization, relation to tumor infiltrating immune cell composition, and prognostic significance in breast cancer using publicly available datasets. Our results suggest an inverse correlation ...
Source: Cancer Immunology, Immunotherapy - August 4, 2020 Category: Cancer & Oncology Source Type: research