Lauss, et al. – Summary

Lauss M, Donia M, Harbst K, Andersen R, Mitra S, Rosengren F, Salim M, Vallon-Christersson J, Törngren T, Kvist A, Ringnér M, Svane IM, Jönsson G. Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma. Nat Commun. 2017 Nov 23;8(1):1738. Available at: https://www.nature.com/articles/s41467-017-01460-0


Higher tumor mutational burden is good for response to adoptive T cell therapy (ACT) in melanoma

Until recently metastatic melanomas were considered difficult to treat but thanks to the recent emergence of immunotherapies, the response rate has increased significantly. Immunotherapies re-energize patient’s own immune system to fight the tumor using different approaches, among which adoptive T cell therapy is a less established method. This therapy came into limelight with the successful treatment of the former US president Ronald Reagan. However, not all melanoma patients get clinical benefit from ACT in the conducted clinical trials. Hence, further improvement of the diagnostic approaches and development of biological markers is necessary for better patient selection for ACT.

Our research focused on the aspect of discovering molecular features of the tumor that could work as suitable biomarker for this kind of treatment. We identified that patients with high number of mutations respond better to ACT. This may be due to the fact that many of these mutations could produce a special type of protein component called neoantigens, which are identified by our immune system as potential threats. Upon identifying these neoantigens, our immune cells especially T cells come in neutralizing the cells that are producing these special protein components and thereby reduce the tumor. This idea was further supported by our findings that predicted neoantigen burden in tumors also associate with clinical benefit and better patient survival. Together, these features could be potentially used as future biomarker for adoptive T cell therapy.

Left hand figure shows basic schematic of ACT, where extracted T cells from patient tumors are cultured and expanded before infusing them in in respective patient body to fight the tumor. Adapted from: Perica K et al., Rambam Maimonides Med J. 2015;6(1):e0004. Right hand figure shows how patients categorized by their tumor mutation burden overall survive, when treated with ACT. Adapted from Lauss et al., Nature Communications volume 8, Article number: 1738 (2017).

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