Although highly successful in other entities, immune checkpoint inhibition has so far only shown limited efficacy in an unselected population of colorectal cancer patients. The particular composition of the inflammatory microenvironment of colorectal cancer, characterized by a low density of tumor-infiltrating-lymphocytes and no PDL1 expression on the tumor cells, might explain this resistance. Indeed, colorectal cancer with microsatellite instability responds much better to immune checkpoint inhibitors and present with a much higher infiltration with T-cells. Dense infiltration with tumor-associated macrophages at the invasion margin is a further characteristic of the inflammatory microenvironment in colorectal cancer potentially causing the limited response to immune checkpoint inhibitors. Interestingly, PDL1 expression can be frequently observed on these tumor-associated macrophages at the invasion margin, which potentially reduce the infiltration with T cells. Interfering with this population of myeloid cells is a possible new immune modulating treatment approach, although more insight on the exact underlying mechanisms causing tumor supportive or suppressive behavior of the myeloid cells is needed. Here, therapeutic approaches combining immune checkpoint inhibitor modulating the T cells function and specific modulators of the tumor-associated macrophages might be successful and should be investigated in future clinical trials.
Listen to the podcast with Professor Niels Halama, MD (Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany) and read the Abstract on the ESMO Open website: https://esmoopen.bmj.com/content/3/5/e000426.