ArticleCell2015
Molecular and genetic properties of tumors associated with local immune cytolytic activity.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2,453 papers, 1 of them a synthesis that pooled it.
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Who cites it
2,453 citing papers in PubMed, 1 synthesis or guideline pooled it, 4,036 citations in OpenAlex.
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2,393 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
How the genomic landscape of a tumor shapes and is shaped by anti-tumor immunity has not been systematically explored. Using large-scale genomic data sets of solid tissue tumor biopsies, we quantified the cytolytic activity of the local immune infiltrate and identified associated properties across 18 tumor types. The number of predicted MHC Class I-associated neoantigens was correlated with cytolytic activity and was lower than expected in colorectal and other tumors, suggesting immune-mediated elimination. We identified recurrently mutated genes that showed positive association with cytolytic activity, including beta-2-microglobulin (B2M), HLA-A, -B and -C and Caspase 8 (CASP8), highlighting loss of antigen presentation and blockade of extrinsic apoptosis as key strategies of resistance to cytolytic activity. Genetic amplifications were also associated with high cytolytic activity, including immunosuppressive factors such as PDL1/2 and ALOX12B/15B. Our genetic findings thus provide evidence for immunoediting in tumors and uncover mechanisms of tumor-intrinsic resistance to cytolytic activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.