Systematic evaluation of immune regulation and modulation

Abstract

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.

Lipoprotein‐associated phospholipase A2: The story continues

“…The ability of PLA2G7 to improve the predictive power of the gene signatures probably results from the regulation of the tumor microenvironment, and an elevated level of PLA2G7 was a predictor of increased survival following anti‐cytotoxic T lymphocyte‐associated antigen‐4 directed therapy . Owing to the autoimmune toxicity induced by immunotherapy, the discovery of the biomarkers, especially blood biomarkers such as PLA2G7 , is valuable and could aid the identification of the subset of patients who can benefit from immunotherapy and simultaneously exhibit low risk for autoimmune toxicity . Furthermore, PLA2G7 was also identified as a diagnostic marker via a microarray technique for profiling the transcriptome of esophageal cancer cells.…”

“…206 Owing to the autoimmune toxicity induced by immunotherapy, the discovery of the biomarkers, especially blood biomarkers such as PLA2G7, is valuable and could aid the identification of the subset of patients who can benefit from immunotherapy and simultaneously exhibit low risk for autoimmune toxicity. 207,208 Furthermore, PLA2G7 was also identified as a diagnostic marker via a microarray technique for profiling the transcriptome of esophageal cancer cells. It was significantly overexpressed in earlier tumor stages of both histological subtypes, namely, esophageal squamous cell carcinoma and esophageal adenocarcinoma.…”

Discovery and application of immune biomarkers for hematological malignancies

“…Neoplastic cells activate gene expression programmes in the TME that are supportive of tumour growth and inherently immune suppressive [4]. The TME is increasingly viewed as an attractive candidate for the discovery of predictive and prognostic immune biomarkers [11,13].…”

“…Challenges to identifying biomarkers have recently been reviewed [10]. Despite the reciprocal relationship between tumours and the patient's immune system, it is presently unknown whether measurements in blood may correlate with findings from tumour sites, including lymph nodes and bone marrow (BM) [3,11]. In this respect, peripheral blood markers reflecting immune function at baseline ("peripheral immunoscore") have successfully predicted progression-free survival (PFS) in patients receiving vaccines for metastatic breast cancer and prostate cancer [12].…”

A primer on recent developments in cancer immunotherapy, with a focus on neoantigen vaccines

“…Urgent efforts are now being made to translate current knowledge and capabilities to the understanding of baseline immunity and response monitoring, and thence the choice of predictive biomarkers [68,211] . Magnetic resonance imaging (MRI) based biomarkers of response to immunotherapy have been recently proposed [212] .…”