Community Series In Unveiling The Tumor Microenvironment By Machine Learning To Develop New Immunotherapeutic Strategies Volume Ii

The tumor microenvironment (TME) plays a critical role in tumor proliferation, progression, and therapeutic responses. TME is a complex network of cancer cells, stromal cells, and, most importantly, infiltrating immune cells. Cancer cells regulate numerous biological functions through direct or indirect interaction with TME components. Emerging evidence suggests that TME crucially influences the response to both chemotherapy and immunotherapy. As scientific research has entered the big data era with the fast development of high-throughput sequencing technologies, machine learning has been gradually widely applied to extract important knowledge from big data bioinformatics. Thus, characterizing the TME landscape in cancer and identifying different immune-related TME phenotypes using machine learning-based bioinformatics analyses, in vitro experiments, and in vivo experiments are of great interest and significance.

The tumor microenvironment (TME) plays a critical role in tumor proliferation, progression, and therapeutic responses. TME is a complex network of cancer cells, stromal cells, and, most importantly, infiltrating immune cells. Cancer cells regulate numerous biological functions through direct or indirect interaction with TME components. Emerging evidence suggests that TME crucially influences the response to both chemotherapy and immunotherapy. As scientific research has entered the big data era with the fast development of high-throughput sequencing technologies, machine learning has been gradually widely applied to extract important knowledge from big data bioinformatics. Thus, characterizing the TME landscape in cancer and identifying different immune-related TME phenotypes using machine learning-based bioinformatics analyses, in vitro experiments, and in vivo experiments are of great interest and significance.

This Research Topic is the second volume of the “Community Series in Novel Biomarkers for Predicting Response to Cancer Immunotherapy". Please see Volume I here. Immunotherapy has revolutionized the treatment of malignancies. Targeting of immune checkpoints cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 (PD-1) and its ligand (PD-L1) has led to improving survival in a subset of patients. Despite their remarkable success, clinical benefit remains limited to only a subset of patients. A significant limitation behind these current treatment modalities is an irregularity in clinical response, which is especially pronounced among checkpoint inhibition. Currently, relevant predictors of cancer immunotherapy response include microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR), expression of PD-L1, tumor mutation burden (TMB), immune genomic characteristics, and tumor infiltrating lymphocytes (TILs). However, none of them have sufficient evidence to be a stratification factor. Moreover, as the combined strategies for effective cancer immunotherapy had been developed in multiple tumors, such as Immunotherapy combined with chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. Therefore, the development of novel biomarkers endowed with high sensitivity, specificity and accuracy able to identify which patients may truly benefit from the treatment with cancer immunotherapy would allow to refine the therapeutic selection and to better tailor the treatment strategy. This research topic aims to focus on the advances in the discoveries of novel biomarkers for predicting response to cancer immunotherapy in various tumors. We welcome the submission of original research and review articles that include biomarkers in clinical study and applications, as well as technologies or discoveries in experimental approaches.

Advances in cancer research have led to an improved understanding of the molecular mechanisms underpinning the development of cancer and how the immune system responds to cancer. This influx of research has led to an increasing number and variety of therapies in the drug development pipeline, including targeted therapies and associated biomarker tests that can select which patients are most likely to respond, and immunotherapies that harness the body's immune system to destroy cancer cells. Compared with standard chemotherapies, these new cancer therapies may demonstrate evidence of benefit and clearer distinctions between efficacy and toxicity at an earlier stage of development. However, there is a concern that the traditional processes for cancer drug development, evaluation, and regulatory approval could impede or delay the use of these promising cancer treatments in clinical practice. This has led to a number of effortsâ€"by patient advocates, the pharmaceutical industry, and the Food and Drug Administration (FDA)â€"to accelerate the review of promising new cancer therapies, especially for cancers that currently lack effective treatments. However, generating the necessary data to confirm safety and efficacy during expedited drug development programs can present a unique set of challenges and opportunities. To explore this new landscape in cancer drug development, the National Academies of Sciences, Engineering, and Medicine developed a workshop held in December 2016. This workshop convened cancer researchers, patient advocates, and representatives from industry, academia, and government to discuss challenges with traditional approaches to drug development, opportunities to improve the efficiency of drug development, and strategies to enhance the information available about a cancer therapy throughout its life cycle in order to improve its use in clinical practice. This publication summarizes the presentations and discussions from the workshop.

In this book we provide insights into liver – cancer and immunology. Experts in the field provide an overview over fundamental immunological questions in liver cancer and tumorimmunology, which form the base for immune based approaches in HCC, which gain increasing interest in the community due to first promising results obtained in early clinical trials. Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death in the United States. Treatment options are limited. Viral hepatitis is one of the major risk factors for HCC, which represents a typical “inflammation-induced” cancer. Immune-based treatment approaches have revolutionized oncology in recent years. Various treatment strategies have received FDA approval including dendritic cell vaccination, for prostate cancer as well as immune checkpoint inhibition targeting the CTLA4 or the PD1/PDL1 axis in melanoma, lung, and kidney cancer. Additionally, cell based therapies (adoptive T cell therapy, CAR T cells and TCR transduced T cells) have demonstrated significant efficacy in patients with B cell malignancies and melanoma. Immune checkpoint inhibitors in particular have generated enormous excitement across the entire field of oncology, providing a significant benefit to a minority of patients.