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Although highly successful in other entities, immune checkpoint inhibition has so far only shown limited efficacy in an unselected population of patients with colorectal cancer. The particular composition of the inflammatory microenvironment of colorectal cancer, characterised by a low density of tumour infiltrating lymphocytes and no PDL1 expression on the tumour cells, might explain this resistance. Indeed, colorectal cancer with microsatellite instability responds much better to immune checkpoint inhibitors and presents with a much higher infiltration with T cells. Dense infiltration with tumour-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 tumour-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 tumour supportive or suppressive behaviour of the myeloid cells is needed. Here, therapeutic approaches combining immune checkpoint inhibitor modulating the T cell function and specific modulators of the tumour-associated macrophages might be successful and should be investigated in future clinical trials.
Competing interests None declared.
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