The effect of organ-specific tumor microenvironments on response patterns to immunotherapy

Abstract

Immunotherapy, particularly immune checkpoint inhibitors, have become widely used in various settings across many different cancer types in recent years. Whilst patients are often treated on the basis of the primary cancer type and clinical stage, recent studies have highlighted disparity in response to immune checkpoint inhibitors at different sites of metastasis, and their impact on overall response and survival. Studies exploring the tumor immune microenvironment at different organ sites have provided insights into the immune-related mechanisms behind organ-specific patterns of response to immunotherapy. In this review, we aimed to highlight the key learnings from clinical studies across various cancers including melanoma, lung cancer, renal cell carcinoma, colorectal cancer, breast cancer and others, assessing the association of site of metastasis and response to immune checkpoint inhibitors. We also summarize the key clinical and pre-clinical findings from studies exploring the immune microenvironment of specific sites of metastasis. Ultimately, further characterization of the tumor immune microenvironment at different metastatic sites, and understanding the biological drivers of these differences, may identify organ-specific mechanisms of resistance, which will lead to more personalized treatment approaches for patients with innate or acquired resistance to immunotherapy.

Dynamic changes in immune cells in humanized liver metastasis and subcutaneous xenograft mouse models

“…In addition to investigating the functional characteristics of immune cells in response to tumors, we should also consider differences in the organ-speci c TME to better combat immunosuppressive tumors. The e cacy of immunotherapy has already been shown to vary depending on the type of cancer, but organ-speci c responses to immunotherapy may also achieve discordant results due to the TME, a phenomenon that was discussed previously 27 . In addition, in patients with advanced hepatocellular carcinoma, the effects of immunotherapy were observed to differ across organs such as the site of the primary tumor, the lung, and the liver 28 .…”