High expression of B7-H3 on stromal cells defines tumor and stromal compartments in epithelial ovarian cancer and is associated with limited immune activation
ConclusionsThis study provides insight into the expression patterns of B7-H3 and B7-H4 in the ovarian TME. Further, we demonstrate an association between the tumor-to-stroma ratio and the phenotype of tumor-infiltrating immune cells. We also find that some but not all immune parameters show consistency between peritoneal metastatic sites. These data have implications for the design of immunotherapies targeting these B7 molecules in epithelial ovarian cancer. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 31, 2019 Category: Cancer & Oncology Source Type: research

Positron emission tomography as an adjuvant diagnostic test in the evaluation of checkpoint inhibitor-associated acute interstitial nephritis
ConclusionsTo our knowledge, this is the first report describing increased18F-flourodeoxyglucose uptake in the renal cortex in a patient with checkpoint inhibitor-associated acute interstitial nephritis. Our findings suggest that18F-flourodeoxyglucose positron-emission tomography may be a valuable test for diagnosing immune-mediated nephritis, particularly in patients where timely kidney biopsy is not feasible. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 21, 2019 Category: Cancer & Oncology Source Type: research

The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC)
AbstractThe approval of immunotherapeutic agents and immunotherapy-based combination strategies in recent years has revolutionized the treatment of patients with advanced renal cell carcinoma (aRCC). Nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor monoclonal antibody, was approved as monotherapy in 2015 for aRCC after treatment with a VEGF-targeting agent. In April 2018, the combination of nivolumab and ipilimumab, a CTLA-4 inhibitor, was approved for intermediate- and poor-risk, previously untreated patients with aRCC. Then, in 2019, combinations therapies consisting of pembrolizumab (anti-PD-1) or avel...
Source: Journal for Immunotherapy of Cancer - December 20, 2019 Category: Cancer & Oncology Source Type: research

Interleukin-15 in cancer immunotherapy: IL-15 receptor complex versus soluble IL-15 in a cancer cell-delivered murine leukemia model
AbstractCytokines of the common γ-chain receptor family such as IL-15 are vital with respect to activating immune cells, sustaining healthy immune functions, and augmenting the anti-tumor activity of effector cells, making them ideal candidates for cancer immunotherapy. IL-15, either in its soluble form (IL-15sol) or complexed wi th IL-15Rα (IL-15Rc), has been shown to exhibit potent anti-tumor activities in various experimental cancer studies. Here we describe the impact of intraperitoneal IL-15 in a cancer cell-delivered IL-15 immunotherapy approach using the 70Z/3-L leukemia mouse model. Whereas both forms o...
Source: Journal for Immunotherapy of Cancer - December 19, 2019 Category: Cancer & Oncology Source Type: research

Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer patients with HIV, hepatitis B, or hepatitis C viral infection
ConclusionsOur retrospective series is one of the largest case series to report clinical outcomes among HIV, HBV and HCV patients treated with ICI therapy. Toxicity and efficacy rates were similar to those observed in patients without chronic viral infections. Viral reactivation was not observed. Tumor responses occurred in HIV patients with low CD4 T-cell counts. While prospective studies are needed to validate above findings, these data support not excluding such patients from ICI –based clinical trials or treatment. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 17, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Impact of antibiotic therapy on the development and response to treatment of immune checkpoint inhibitor-mediated diarrhea and colitis
Following publication of the original article [1], the authors have reported that an author ’s name has been incorrectly spelled: the correct given name is Anne-Marie (instead of Anne-Maria P) and family name is Chaftari. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 17, 2019 Category: Cancer & Oncology Source Type: research

Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine
ConclusionsAltogether, these results identify PS and PD as novel ICD inducers that could be effectively combined with PDT in cancer therapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 16, 2019 Category: Cancer & Oncology Source Type: research

High OX-40 expression in the tumor immune infiltrate is a favorable prognostic factor of overall survival in non-small cell lung cancer
ConclusionsHigh OX-40 IHC expression in the tumor immune infiltrate is associated with favorable prognosis and increased levels of immune-related genes including IFN-gamma in patients with surgically resected stage I-III NSCLC. Its prognostic utility is independent of PD-L1 and other common markers of immune activation. High OX-40 expression potentially identifies a unique subgroup of NSCLC that may benefit from co-stimulation with OX-40 agonist antibodies and potentially enhance the efficacy of existing immune checkpoint therapies. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 16, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Immunostimulatory RNA leads to functional reprogramming of myeloid-derived suppressor cells in pancreatic cancer
Following publication of the original article [1], the authors have reported that Fig.  2 and Additional file 1: Figure S1, S2 partially show red scripts. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 16, 2019 Category: Cancer & Oncology Source Type: research

Genetic instability as a driver for immune surveillance
ConclusionsThese two main results indicate a potential role of genetic instability as a driver of transitions towards immune control of tumors, as well as the effectiveness of increasing mutational loads prior to adoptive cell therapies. This mathematical framework is therefore a quantitative step towards predicting the outcomes of combined therapies where genetic instability might play a key role. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 11, 2019 Category: Cancer & Oncology Source Type: research

Blocking CD47 efficiently potentiated therapeutic effects of anti-angiogenic therapy in non-small cell lung cancer
ConclusionsOur research provided evidence that CD47 blockade could sensitize NSCLC to anti-angiogenic therapy and potentiate its anti-tumor effects by enhancing macrophage infiltration and tumor cell destruction, providing novel therapeutics for NSCLC by disrupting CD47/SIRP α interaction and angiogenetic axis. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 11, 2019 Category: Cancer & Oncology Source Type: research

Chemotherapy accelerates immune-senescence and functional impairments of V δ2 pos T cells in elderly patients affected by liver metastatic colorectal cancer
AbstractHuman (gamma delta) γδ T cells are unconventional innate-like lymphocytes displaying a broad array of anti-tumor activities with promising perspectives in cancer immunotherapy. In this context, Vδ2pos T cells represent the preferential target of several immunotherapy protocols against solid tumors. However, the impact of both aging and chemotherapy (CHT) on V δ2pos T cells is still unknown. The present study evaluates with multi-parametric flow cytometry the frequencies, terminal differentiation, senescence and effector-functions of peripheral blood and tumor infiltrating V δ2pos T cel...
Source: Journal for Immunotherapy of Cancer - December 11, 2019 Category: Cancer & Oncology Source Type: research

Development of a prognostic composite cytokine signature based on the correlation with nivolumab clearance: translational PK/PD analysis in patients with renal cell carcinoma
This report outlines a translational PK-pharmacodynamic (PD) methodology used to derive a baseline composite cytokine signature correlated with nivolumab clearance using data from three clinical trials in which nivolumab or everolimus was administered.MethodsPeripheral serum cytokine (PD) and nivolumab clearance (PK) data from patients with RCC were analyzed using a PK-PD machine-learning model. Nivolumab studies CheckMate 009 (NCT01358721) and CheckMate 025 (NCT01668784) (n = 480) were used for PK-PD analysis model development and cytokine feature selection (training dataset). Validation of the model and asses...
Source: Journal for Immunotherapy of Cancer - December 11, 2019 Category: Cancer & Oncology Source Type: research

Combined innate and adaptive immunotherapy overcomes resistance of immunologically cold syngeneic murine neuroblastoma to checkpoint inhibition
ConclusionsThese data suggest that a combined innate and adaptive immunotherapeutic approach can be effective against immunologically cold syngeneic murine neuroblastoma. Further testing is needed to determine how these concepts might translate into development of more effective immunotherapeutic approaches for the treatment of clinically high-risk neuroblastoma. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 6, 2019 Category: Cancer & Oncology Source Type: research

Tumor microenvironment-derived S100A8/A9 is a novel prognostic biomarker for advanced melanoma patients and during immunotherapy with anti-PD-1 antibodies
AbstractBackgroundPredicting metastasis in melanoma patients is important for disease management and could help to identify those who might benefit from adjuvant treatment. The aim of this study was to investigate whether the tumor microenvironment-derived protein S100A8/A9 qualifies as prognostic marker for melanoma patients, also in the setting of immunotherapy.MethodsS100A8/A9 gene and protein expression were analyzed on melanocytic nevi, primary melanomas and metastases using a cDNA library and three independent tissue-microarrays (TMA). Serum levels of S100A8/A9 were measured using a specific ELISA in two independent ...
Source: Journal for Immunotherapy of Cancer - December 5, 2019 Category: Cancer & Oncology Source Type: research

A phase Ib study of utomilumab (PF-05082566) in combination with mogamulizumab in patients with advanced solid tumors
ConclusionsThe combination of utomilumab/mogamulizumab was safe and tolerable, and may be suitable for evaluation in settings where CCR4-expressing Tregs are suppressing anticancer immunity.Trial registrationClinicalTrials.gov identifier:NCT02444793. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 4, 2019 Category: Cancer & Oncology Source Type: research

Tumor microenvironment dictates regulatory T cell phenotype: Upregulated immune checkpoints reinforce suppressive function
ConclusionsWe demonstrate that the TME confers a suppressive function on Treg cells by upregulating IC-molecule expression. Targeting IC-molecules, including PD-1, on Treg cells may be effective for cancer treatment. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 4, 2019 Category: Cancer & Oncology Source Type: research

Functional characterization of the selective pan-allele anti-SIRP α antibody ADU-1805 that blocks the SIRPα–CD47 innate immune checkpoint
ConclusionsBlocking the SIRP α-CD47 interaction via SIRPα, while similarly efficacious in vitro, differentiates ADU-1805 from CD47-targeting agents with respect to safety and absence of inhibition of T-cell activation. The data presented herein support further advancement of ADU-1805 towards clinical development. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 4, 2019 Category: Cancer & Oncology Source Type: research

Incidence rates of immune-related adverse events and their correlation with response in advanced solid tumours treated with NIVO or NIVO+IPI: a systematic review and meta-analysis
AbstractBackgroundDeciphering the correlation between immune-related adverse events (irAEs) categorized by organ system class and clinical benefit of immunotherapy is critical for clinical practice. The aim of this study is to investigate the incidence rates of irAEs and their correlations with objective response rate (ORR) in patients with advanced solid tumours treated with nivolumab (NIVO) or nivolumab plus ipilimumab (NIVO+IPI).MethodsPubMed, Embase and Cochrane library were searched for eligible studies from January 1st, 2000 to May 1st 2019. Published clinical trials on NIVO or NIVO+IPI with reported irAEs were inclu...
Source: Journal for Immunotherapy of Cancer - December 4, 2019 Category: Cancer & Oncology Source Type: research

Rapid and sustained response to immune checkpoint inhibition in cutaneous squamous cell carcinoma after allogenic hematopoietic cell transplant for s ézary syndrome
ConclusionThis is the first case to our knowledge of rapid and durable response of both cSCC and CTCL to immune checkpoint inhibition after allo-HCT. Although this report highlights the potential for significant response to this class of medication, further studies are required to confirm the efficacy and safety of this approach in patients with CTCL after allo-HCT given the potential concern of GVHD. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 4, 2019 Category: Cancer & Oncology Source Type: research

Worsening and newly diagnosed paraneoplastic syndromes following anti-PD-1 or anti-PD-L1 immunotherapies, a descriptive study
AbstractBackgroundParaneoplastic syndromes (PNS) are autoimmune disorders specifically associated with cancer. There are few data on anti-PD-1 or anti-PD-L1 immunotherapy in patients with a PNS. Our objective was to describe the outcome for patients with a pre-existing or newly diagnosed PNS following the initiation of anti-PD-1 or anti-PD-L1 immunotherapy.MethodsWe included all adult patients (aged ≥18) treated with anti-PD-1 or anti-PD-L1 immunotherapy for a solid tumor, diagnosed with a PNS, and registered in French pharmacovigilance databases. Patients were allocated to cohorts 1 and 2 if the PNS had been diagnosed ...
Source: Journal for Immunotherapy of Cancer - December 3, 2019 Category: Cancer & Oncology Source Type: research

Multiple nivolumab-induced CNS demyelination with spontaneous resolution in an asymptomatic metastatic melanoma patient
ConclusionWe report the first case of a melanoma patient with an asymptomatic and spontaneously reversible central nervous system demyelination following nivolumab immunotherapy. This case highlights the need for better recognition of such atypical and rare neurological toxicities which could be mistaken for progressive brain metastases. Early recognition and appropriate management are crucial to reduce severity and duration of these toxicities, especially for patients with less favourable evolution. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 2, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Pericardial effusion under nivolumab: case-reports and review of the literature
Following publication of the original article [1], the authors reported that authors ’ given and family names haven been incorrectly tagged. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - December 2, 2019 Category: Cancer & Oncology Source Type: research

Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge 2018” (28–29 November, 2018, Naples, Italy)
AbstractImmunotherapy is now widely established as a potent and effective treatment option across several types of cancer. However, there is increasing recognition that not all patients respond to immunotherapy, focusing attention on the immune contexture of the tumor microenvironment (TME), drivers of the immune response and mechanisms of tumor resistance to immunity. The development of novel immunotherapeutics and their use in combination with checkpoint inhibitors and other standard of care and novel treatment modalities is an area of particular attention across several tumor types, including melanoma, lung, ovarian, br...
Source: Journal for Immunotherapy of Cancer - November 29, 2019 Category: Cancer & Oncology Source Type: research

Angiogenesis and immune checkpoint inhibitors as therapies for hepatocellular carcinoma: current knowledge and future research directions
AbstractHepatocellular carcinoma (HCC) is the second deadliest cancer worldwide, due to its high incidence and poor prognosis. Frequent initial presentation at advanced stages along with impaired liver function limit the use of a broad therapeutic arsenal in patients with HCC. Although main HCC oncogenic drivers have been deciphered in recent years (TERT, TP53, CTNNB1 mutations, miR122 and CDKN2A silencing), therapeutic applications derived from this molecular knowledge are still limited. Given its high vascularization and immunogenicity, antiangiogenics and immune checkpoint inhibitors (ICI), respectively, are two therape...
Source: Journal for Immunotherapy of Cancer - November 29, 2019 Category: Cancer & Oncology Source Type: research

PD1 Hi CD8 + T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma
ConclusionThe current study unveils the unique features of PD1Hi CD8+ exhausted T cells in HCC, and also suggests that exhausted T cells could act as a biomarker to select the most care-demanding patients for tailored therapies. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 29, 2019 Category: Cancer & Oncology Source Type: research

Soluble immune checkpoint-related proteins as predictors of tumor recurrence, survival, and T cell phenotypes in clear cell renal cell carcinoma patients
AbstractBackgroundImmune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. With the exception of a few candidate biomarkers, the prognostic role of soluble immune checkpoint-related proteins in clear cell renal cell cancer (ccRCC) patients is largely uninvestigated.MethodsWe profiled the circulating levels of 14 immune checkpoint-related proteins panel (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, CD137, CD27 and CTLA-4) and their associations with the risk of recurrence and death in 182 ccRCC patients using a multiplex Luminex assay. Gene expression in tumors from a...
Source: Journal for Immunotherapy of Cancer - November 29, 2019 Category: Cancer & Oncology Source Type: research

Longitudinal immune characterization of syngeneic tumor models to enable model selection for immune oncology drug discovery
ConclusionsTaken together, this dataset will provide a framework for characterization and enable the selection of the optimal models for immunotherapy combinations and generate potential biomarkers for clinical evaluation in identifying responders and non-responders to immunotherapy combinations. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 28, 2019 Category: Cancer & Oncology Source Type: research

MDM2 inhibitor APG-115 synergizes with PD-1 blockade through enhancing antitumor immunity in the tumor microenvironment
ConclusionOur results demonstrate that p53 activation mediated by APG-115 promotes antitumor immunity in the tumor microenvironment (TME) regardless of theTrp53 status of tumors per se. Instead, such an effect depends on p53 activation inTrp53 wild-type immune cells in the TME. Based on the data, a phase 1b clinical trial has been launched for the evaluation of APG-115 in combination with pembrolizumab in solid tumor patients including those withTP53mut tumors. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 28, 2019 Category: Cancer & Oncology Source Type: research

Expanding CAR T cells in human platelet lysate renders T cells with in vivo longevity
ConclusionsOur study highlights the importance of serum choice in the generation of CAR T cells for clinical use. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 28, 2019 Category: Cancer & Oncology Source Type: research

Immunotherapy response evaluation with magnetic resonance elastography (MRE) in advanced HCC
AbstractBackgroundCurrently, there are no imaging predictors of immunotherapy outcome in hepatocellular carcinoma (HCC). The study aim was to determine if stiffness changes measured by magnetic resonance elastography (MRE) can be a predictor of immunotherapy response in patients with advanced HCC.Materials and methodsThis was a prospective study of 15 patients with biopsy proven-advanced HCC treated with Pembrolizumab. All patients had liver MRE and liver biopsy at baseline and at 6  weeks of therapy. Change in HCC stiffness on MRE was compared with overall survival (OS), time to disease progression (TTP), and numbe...
Source: Journal for Immunotherapy of Cancer - November 28, 2019 Category: Cancer & Oncology Source Type: research

IL-17 inhibits CXCL9/10-mediated recruitment of CD8 + cytotoxic T cells and regulatory T cells to colorectal tumors
ConclusionIL-17 signals to colorectal tumor cells and inhibits their production of CXCL9/10 chemokines. By doing so, IL-17 inhibits the infiltration of CD8+ CTLs and Tregs to CRC, thus promoting CRC development. Cancer immunotherapy may be benefited by the use of anti-IL-17 agents as adjuvant therapies, which serve to block both IL-17-mediated tumor promotion and T cell exclusion. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 27, 2019 Category: Cancer & Oncology Source Type: research

Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth
ConclusionsGDNPs can alter M2 polarization both in vitro and in vivo, which contributes to an antitumor response. The polarization of macrophages induced by GDNPs is largely dependent on TLR4 and MyD88 signalling. GDNPs as an immunomodulator participate in mammalian immune response and may represent a new class of nano-drugs in cancer immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 27, 2019 Category: Cancer & Oncology Source Type: research

Peripheral immune-based biomarkers in cancer immunotherapy: can we realize their predictive potential?
AbstractThe immunologic landscape of the host and tumor play key roles in determining how patients will benefit from immunotherapy, and a better understanding of these factors could help inform how well a tumor responds to treatment. Recent advances in immunotherapy and in our understanding of the immune system have revolutionized the treatment landscape for many advanced cancers. Notably, the use of immune checkpoint inhibitors has demonstrated durable responses in various malignancies. However, the response to such treatments is variable and currently unpredictable, the availability of predictive biomarkers is limited, a...
Source: Journal for Immunotherapy of Cancer - November 27, 2019 Category: Cancer & Oncology Source Type: research

TLR9 activation cooperates with T cell checkpoint blockade to regress poorly immunogenic melanoma
AbstractTumors that lack pre-existing immune infiltration respond poorly to T cell checkpoint blockade immunotherapy. These cancers often surround themselves with high densities of suppressive myeloid stroma while excluding immunostimulatory dendritic cells. Tumor-resident myeloid cells and selected lymphocyte populations retain expression of Toll-like Receptors (TLR) that sense common features of pathogens and activate innate immunity in response. We explored whether agonists of TLR9 could augment innate immunity to promote tumor regression alone or in combination with T cell checkpoint blockade. In the setting of the imm...
Source: Journal for Immunotherapy of Cancer - November 26, 2019 Category: Cancer & Oncology Source Type: research

Sarcosine promotes trafficking of dendritic cells and improves efficacy of anti-tumor dendritic cell vaccines via CXC chemokine family signaling
ConclusionSarcosine increases the migration of murine and human DCs via the CXC chemokine pathway. This platform can be utilized to improve existing DC vaccine strategies. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 21, 2019 Category: Cancer & Oncology Source Type: research

Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer
AbstractBackgroundBone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy.MethodsPretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM.ResultsCohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squam...
Source: Journal for Immunotherapy of Cancer - November 21, 2019 Category: Cancer & Oncology Source Type: research

Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition
ConclusionsHBV reactivation occurs in a subset of HBsAg-positive cancer patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy. Regular monitoring of HBV DNA and antiviral prophylaxis are advised to prevent this potentially fatal complication. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 21, 2019 Category: Cancer & Oncology Source Type: research

Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer
We describe the pharmacokinetics (PK), exposure-safety, and immunogenicity of atezolizumab in pediatric and young adults with metastatic solid tumors or hematologic malignancies enrolled in this study.MethodsPatients aged
Source: Journal for Immunotherapy of Cancer - November 21, 2019 Category: Cancer & Oncology Source Type: research

BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19 high B lymphocytes
ConclusionsBTLA detected in cancerous tissues can predict poor outcome of EOC patients. Inhibition of BTLA combined with chemotherapy can elevate immune activation and generate potent anti-tumor effects. Thus, the combination of chemotherapy and anti-BTLA antibody may hold potential clinical application for the treatment of EOC patients.Trial registrationThe Trial Registration Number wasNCT00854399. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 21, 2019 Category: Cancer & Oncology Source Type: research

Immune checkpoint inhibitor related myasthenia gravis: single center experience and systematic review of the literature
ConclusionsMG is a life-threatening adverse event of acute onset and rapid progression after ICI initiation. Early use of IVIG or PLEX, regardless of initial symptoms severity, may lead to better outcomes than steroids alone. Our data suggest the need to reassess the current recommendations for management of ICI-related MG until prospective longitudinal studies are conducted to establish the ideal management approach for these patients. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 21, 2019 Category: Cancer & Oncology Source Type: research

Bi- and tri-valent T cell engagers deplete tumour-associated macrophages in cancer patient samples
ConclusionsThis study is the first to achieve selective depletion of specific M2-like macrophage subsets, opening the possibility of eradicating cancer-supporting TAMs whilst sparing those with anti-tumour potential. Targeted TAM depletion with T cell engager-armed EnAd offers a powerful therapeutic approach combining direct cancer cell cytotoxicity with reversal of immune suppression. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 21, 2019 Category: Cancer & Oncology Source Type: research

Severe early hepatitis B reactivation in a patient receiving anti-CD19 and anti-CD22 CAR T cells for the treatment of diffuse large B-cell lymphoma
ConclusionsOur study provides the first report of the severe, early reactivation of an inactive HBsAg carrier after CAR T cell therapy in DLBCL.Trial registrationChiCTR-OPN-16008526. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 21, 2019 Category: Cancer & Oncology Source Type: research

Radiation myelitis after pembrolizumab administration, with favorable clinical evolution and safe rechallenge: a case report and review of the literature
ConclusionThe confinement within the radiation field and the latency of appearance are suggestive of delayed radiation myelopathy. Nevertheless, the relatively low dose of radiation received and the full recovery after pembrolizumab discontinuation and steroid therapy plead for the contribution of both radiotherapy and immunotherapy in the causality of this complication, as an enhanced inflammatory reaction on a focal post-radiation chronic inflammatory state. In the three previously described cases of myelopathy occurring after radiotherapy and immunotherapy, a complete recovery had not been obtained and the immunotherapy...
Source: Journal for Immunotherapy of Cancer - November 21, 2019 Category: Cancer & Oncology Source Type: research

Immune induction strategies to enhance responses to PD-1 blockade: lessons from the TONIC trial
AbstractProgrammed cell death protein 1 (PD-1) blockade is only effective in a minority of patients, prompting the search for combinatorial therapies that increase responses. Identifying effective combinations requires lengthy testing and so far has shown few successes. To accelerate progress Voorwerk and colleagues (Nat Med. 25(6):920-8, 2019) used an adaptive trial design to compare 4 short-course therapies (radiotherapy, cyclophosphamide, cisplatin and doxorubicin) for their ability to improve the tumor immune microenvironment and enhance responses to subsequent PD-1 blockade in women with metastatic triple negative bre...
Source: Journal for Immunotherapy of Cancer - November 21, 2019 Category: Cancer & Oncology Source Type: research

Peritumoral administration of DRibbles-pulsed antigen-presenting cells enhances the antitumor efficacy of anti-GITR and anti-PD-1 antibodies via an antigen presenting independent mechanism
ConclusionsOverall, these results demonstrate that peritumoral DR-pulsed-BMC/DC administration synergizes with GITR agonist and PD-1 blockade to locally modulate and sustain tumor effector T-cell responses independently of T cell priming and perhaps through innate inflammatory modulations mediated by the DRibbles adjuvant. We offer a unique approach to modify the tumor microenvironment to benefit T-cell-targeted immunotherapies. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 20, 2019 Category: Cancer & Oncology Source Type: research

Calreticulin exposure correlates with robust adaptive antitumor immunity and favorable prognosis in ovarian carcinoma patients
ConclusionsOur data indicate that CALR levels in primary and metastatic HGSC samples have robust prognostic value linked to the activation of clinically-relevant innate and adaptive anticancer immune responses. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 20, 2019 Category: Cancer & Oncology Source Type: research

Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment
ConclusionsOnly 3 out of 612 non-silent mutations encoded for neoantigens that were detectable by MS. Although MS has sensitivity limits and biases, and likely underestimated the true neoantigen burden, this established a lower bound of the percentage of non-silent mutations that encode for presented neoantigens, which may be as low as 0.5%. This could be a reason for the poor responses of non-hypermutated CRCs to immune checkpoint inhibitors. MEK-inhibitors recently failed to improve checkpoint-inhibitor efficacy in CRC and the observed lack of HLA upregulation or improved peptide presentation may explain this. (Source: J...
Source: Journal for Immunotherapy of Cancer - November 18, 2019 Category: Cancer & Oncology Source Type: research

A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer
ConclusionThus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 15, 2019 Category: Cancer & Oncology Source Type: research

Mechanisms regulating PD-L1 expression on tumor and immune cells
ConclusionsMultiple cytokines found in an immune-reactive TME may induce PD-L1 expression on tumor and/or immune cells through distinct signaling mechanisms. Factors driving constitutive PD-L1 expression were not identified in this study. Understanding complex mechanisms underlying PD-L1 display in the TME may allow treatment approaches mitigating expression of this immunosuppressive ligand, to enhance the impact of PD-1 blockade. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - November 15, 2019 Category: Cancer & Oncology Source Type: research