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Cancer immunotherapies are showing promising clinical results in a variety of malignancies. Monitoring the immune as well as the tumor response following these therapies has led to significant advancements in the field. Moreover, the identification and assessment of both predictive and prognostic biomarkers has become a key component to advancing these therapies. Thus, it is critical to develop systematic approaches to monitor the immune response and to interpret the data obtained from these assays. In order to address these issues and make recommendations to the field, the Society for Immunotherapy of Cancer reconvened the Immune Biomarkers Task Force. As a part of this Task Force, Working Group 3 (WG3) consisting of multidisciplinary experts from industry, academia, and government focused on the systematic assessment of immune regulation and modulation. In this review, the tumor microenvironment, microbiome, bone marrow, and adoptively transferred T cells will be used as examples to discuss the type and timing of sample collection. In addition, potential types of measurements, assays, and analyses will be discussed for each sample. Specifically, these recommendations will focus on the unique collection and assay requirements for the analysis of various samples as well as the high-throughput assays to evaluate potential biomarkers. [ABSTRACT FROM AUTHOR]

Harnessing the immune system and preventing immune escape, the immunotherapy of cancer provides great potential for clinical application, in broad patient populations, achieving both conventional and unconventional clinical responses. After the substantial advances in melanoma, the focus of cancer immunotherapy has expanded to include many other cancers. Targeting immune checkpoints and further mechanisms used by tumors to avoid anticancer immunity, different approaches are under evaluation, including combination therapies. The first Immunotherapy Bridge meeting focused on various cancer types including melanoma, non-small cell lung cancer, renal cell, breast and ovarian carcinoma, and discussed mechanisms of action of single agents and combination strategies, and the prediction of clinical responses. [ABSTRACT FROM AUTHOR]

The article provides an analysis of cancer immunotherapy trials and mentions need of rapid and efficient cancer drug development, development of multiple single-agent cancer immunotherapies, and precision medicine.

The Common Rule is a set of ethical principles that provide guidance on the management of human subjects taking part in biomedical and behavioral research in the United States. The elements of the Common Rule were initially developed in 1981 following a revision of the Declaration of Helsinki in 1975. Most academic facilities follow the Common Rule in the regulation of clinical trials research. Recently, the government has suggested a revision of the Common Rule to include more contemporary and streamlined oversight of clinical research. In this commentary, the leadership of the Society for Immunotherapy of Cancer (SITC) provides their opinion on this plan. While the Society recognizes the considerable contribution of clinical research in supporting progress in tumor immunotherapy and supports the need for revisions to the Common Rule, there is also some concern over certain elements which may restrict access to biospecimens and clinical data at a time when high throughput technologies, computational biology and assay standardization is allowing major advances in understanding cancer biology and providing potential predictive biomarkers of immunotherapy response. The Society values its professional commitment to patients for improving clinical outcomes with tumor immunotherapy and supports continued discussion with all stakeholders before implementing changes to the Common Rule in order to ensure maximal patient protections while promoting continued clinical research at this historic time in cancer research. [ABSTRACT FROM AUTHOR]

The Tumor Inflammation Signature (TIS) is an investigational use only (IUO) 18-gene signature that measures a pre-existing but suppressed adaptive immune response within tumors. The TIS has been shown to enrich for patients who respond to the anti-PD1 agent pembrolizumab. To explore this immune phenotype within and across tumor types, we applied the TIS algorithm to over 9000 tumor gene expression profiles downloaded from The Cancer Genome Atlas (TCGA). As expected based on prior evidence, tumors with known clinical sensitivity to anti-programmed cell death protein 1 (PD-1) blockade had higher average TIS scores. Furthermore, TIS scores were more variable within than between tumor types, and within each tumor type a subset of patients with elevated scores was identifiable although with different prevalence associated with each tumor type, the latter consistent with the observed clinical responsiveness to anti PD-1 blockade. Notably, TIS scores only minimally correlated with mutation load in most tumors and ranking tumors by median TIS score showed differing association to clinical sensitivity to PD-1/PD-1 ligand 1 (PD-L1) blockade than ranking of the same tumors by mutation load. The expression patterns of the TIS algorithm genes were conserved across tumor types yet appeared to be minimally prognostic in most cancers, consistent with the TIS score serving as a pan-cancer measurement of the inflamed tumor phenotype. Characterization of the prevalence and variability of TIS will lead to increased understanding of the immune status of untreated tumors and may lead to improved indication selection for testing immunotherapy agents. [ABSTRACT FROM AUTHOR]

Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors and are largely dependent upon the pre-existing immune contexture of individual cancers. Available data suggest that three landscapes best define the cancer microenvironment: immune-active, immune-deserted and immune-excluded. This trichotomy is observable across most solid tumors (although the frequency of each landscape varies depending on tumor tissue of origin) and is associated with cancer prognosis and response to checkpoint inhibitor therapy (CIT). Various gene signatures (e.g. Immunological Constant of Rejection - ICR and Tumor Inflammation Signature - TIS) that delineate these landscapes have been described by different groups. In an effort to explain the mechanisms of cancer immune responsiveness or resistance to CIT, several models have been proposed that are loosely associated with the three landscapes. Here, we propose a strategy to integrate compelling data from various paradigms into a "Theory of Everything". Founded upon this unified theory, we also propose the creation of a task force led by the Society for Immunotherapy of Cancer (SITC) aimed at systematically addressing salient questions relevant to cancer immune responsiveness and immune evasion. This multidisciplinary effort will encompass aspects of genetics, tumor cell biology, and immunology that are pertinent to the understanding of this multifaceted problem. [ABSTRACT FROM AUTHOR]