Spatiotemporal evolution of the clear cell renal cell carcinoma microenvironment links intra-tumoral heterogeneity to immune escape - Genome Medicine

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A study published in GenomeMedicine finds that genetic and immune heterogeneity jointly co-evolve and influence response to immune checkpoint inhibitor in clear cell renal carcinoma.

: Table S1). Our integrated analysis demonstrated that ITH is highly correlated among genomic, transcriptomic, and TME characteristics. ITH-high tumors are enriched for features including SETD2 and PBRM1 mutations, HLA loss of heterozygosity , and CDKN2A/B loss. Immunologically, ITH-high tumors display a depletion of putative neoantigens, elevated myeloid activation, and reduced T cell diversity that are in aggregate associated with escape from the anti-tumor immune response.

Detailed clinical data and treatment regimen for each patient is included in Additional file: Table S2. After obtaining informed consent for tissue collection, samples were directly obtained from the operating room during nephrectomy. At the time of specimen extraction, samples of around 1–1.5 cm were obtained by the treating surgeon from spatially distinct tumor regions and each one labeled according to its spatial location .

 

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