Understanding the tumor immune microenvironment (TIME) for effective therapy

Abstract

The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory. Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic intervention; however, many more patients have experienced minimal or no clinical benefit when provided the same treatment. As technology has advanced, so has the understanding of the complexity and diversity of the immune context of the tumor microenvironment and its influence on response to therapy. It has been possible to identify different subclasses of immune environment that have an influence on tumor initiation and response and therapy; by parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.

Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis

“…Postulated mechanisms for the differential effect of BRM polymorphisms on risk and outcome may lie in how tobacco smoking alters the tumor immune microenvironment (ie, suppressive or active) which can mediate patients’ risk or prognosis . This altered environment provides a milieu that leads to a protective effect of MPM development in the presence of the homozygous variants that repress BRM expression.…”

“…Interactions between genetic polymorphisms and environmental factors, such as tobacco exposure, have been associated with increased risk of developing many malignancies . Although smoking is not considered a classical risk factor for MPM, smoking may change the tumor‐associated immune microenvironment that may alter MPM susceptibility and prognosis . Thus, identifying environmental factors such as smoking that interact with BRM polymorphisms may improve the ability to predict MPM outcomes and more accurately personalize treatment.…”

Nanomedicine‐Based Immunotherapy for the Treatment of Cancer Metastasis

“…[1] Primary tumor, metastatic site, and blood/lymphatic vasculature systems are three major places where these immune cells interact with cancer cells. A primary tumor is typically constituted of cancer cells and many other stromal cells such as dendritic cells (DCs), CTLs, NK cells, regulatory T (T reg ) cells, myeloid-derived suppressor cells (MDSCs), macrophages, and fibroblasts, [56] and is under constant evolution but remains immunosuppressive as a consequence of immune editing. [36,57,58] The cancer cells also acquire invasive capability, as a result of epithelial-mesenchymal transition (EMT) partially triggered by transforming growth factor-β (TGF-β).…”

Intersection of the p63 and NF‐κB pathways in epithelial homeostasis and disease

“…The immune cell profile of the TME, which is comprised of innate and adaptive immune cells, not only contributes to the outgrowth of the tumor but is often predictive of treatment outcome . The influence of p63 on cells of the adaptive immune response was demonstrated in a study by Kubo et al in which p63 was linked to TARC/CCL17 production, which acts as a chemoattractant of CD4+ T lymphocyte populations with broad‐ranging activities.…”