OncoImmunology 

About: OncoImmunology is an academic journal published by Landes Bioscience. The journal publishes majorly in the area(s): Immune system & Immunotherapy. It has an ISSN identifier of 2162-4011. It is also open access. Over the lifetime, 3427 publications have been published receiving 106241 citations. The journal is also known as: Oncoimmunology.

Consensus guidelines for the detection of immunogenic cell death

Abstract: Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.

Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC

Abstract: Dendritic cell-derived exosomes (Dex) are small extracellular vesicles secreted by viable dendritic cells. In the two phase-I trials that we conducted using the first generation of Dex (IFN-γ-free) in end-stage cancer, we reported that Dex exerted natural killer (NK) cell effector functions in patients. A second generation of Dex (IFN-γ-Dex) was manufactured with the aim of boosting NK and T cell immune responses. We carried out a phase II clinical trial testing the clinical benefit of IFN-γ-Dex loaded with MHC class I- and class II-restricted cancer antigens as maintenance immunotherapy after induction chemotherapy in patients bearing inoperable non-small cell lung cancer (NSCLC) without tumor progression. The primary endpoint was to observe at least 50% of patients with progression-free survival (PFS) at 4 mo after chemotherapy cessation. Twenty-two patients received IFN-γ-Dex. One patient exhibited a grade three hepatotoxicity. The median time to progression was 2.2 mo and median overall survival (OS) was 15 mo. Seven patients (32%) experienced stabilization of >4 mo. The primary endpoint was not reached. An increase in NKp30-dependent NK cell functions were evidenced in a fraction of these NSCLC patients presenting with defective NKp30 expression. Importantly, MHC class II expression levels of the final IFN-γ-Dex product correlated with expression levels of the NKp30 ligand BAG6 on Dex, and with NKp30-dependent NK functions, the latter being associated with longer progression-free survival. This phase II trial confirmed the capacity of Dex to boost the NK cell arm of antitumor immunity in patients with advanced NSCLC.

Myeloid derived suppressor cells: Targets for therapy

Abstract: The goal of achieving measurable response with cancer immunotherapy requires counteracting the immunosuppressive characteristics of tumors. One of the mechanisms that tumors utilize to escape immunosurveillance is the activation of myeloid derived suppressor cells (MDSCs). Upon activation by tumor-derived signals, MDSCs inhibit the ability of the host to mount an anti-tumor immune response via their capacity to suppress both the innate and adaptive immune systems. Despite their relatively recent discovery and characterization, anti-MDSC agents have been identified, which may improve immunotherapy efficacy.

Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death.

Abstract: Established tumors are typified by an immunosuppresive microenvironment Countering this naturally occurring phenomenon, emerging evidence suggests that radiation promotes a proimmunogenic milieu within the tumor capable of stimulating host cancer-specific immune responses Three cryptic immunogenic components of cytotoxic-agent induced cell death—namely, calreticulin cell surface exposure, the release of high mobility group box 1 (HMGB1) protein, and the liberation of ATP—have been previously shown to be critical for dendritic cell (DC) activation and effector T-cell priming Thus, these immune-mobilizing components commonly presage tumor rejection in response to treatment We initially set out to address the hypothesis that radiation-induced immunogenic cell death (ICD) is dose-dependent Next, we hypothesized that radiation would enhance chemotherapy-induced ICD when given concomitantly, as suggested by the favorable clinical outcomes observed in response to analogous concurrent chemoradiation regimens Thus, we designed an in vitro assay to examine the 3 hallmark features of ICD at clinically relevant doses of radiation We then tested the immunogenic-death inducing effects of radiation combined with carboplatin or paclitaxel, focusing on these combinations to mimic chemoradiation regimens actually used in clinical trials of early stage triple negative [NCT0128953/NYU-10–01969] and locally advanced [NYU-06209] breast cancer patients, respectively Despite the obvious limitations of an in vitro model, radiotherapy produced both a dose-dependent induction and chemotherapeutic enhancement of ICD These findings provide preliminary evidence that ICD stimulated by either high-dose radiotherapy alone, or concurrent chemoradiation regimens, may contribute to the establishment of a peritumoral proimmunogenic milieu

Targeting PD-1/PD-L1 interactions for cancer immunotherapy.

Abstract: Tumors have developed multiple immunosuppressive mechanisms to turn down the innate and the effector arms of the immune system, thus compromising most of the immunotherapeutic strategies that have been proposed during the last decade Right after the pioneering success of Ipilimumab (anti-CTLA4) in metastatic melanoma, several groups have conducted trials aiming at subverting other immune checkpoints Two articles that recently appeared in the New England Journal of Medicine1,2 highlight the therapeutic potential of agents that target PD-1 or its ligand PD-L1 in patients with advanced cancer, even individuals with lung or brain metastases If confirmed, this clinical breakthrough will open novel avenues for cancer immunotherapy