Melanoma, Mutations, and Mice

MELANOMAS with mutations in ATR, a protein that detects and repairs DNA damage caused by ultraviolet exposure and which contributes to cell reproduction, have recently been found to have an altered immune environment that promotes the growth of tumours. Researchers hope that these findings will help improve immunotherapies for melanoma and successfully discern the patients who will be more likely to respond to such treatments. With melanoma accounting for the majority of deaths from skin cancer, this finding is highly relevant.

The senior study author, Prof Anand Ganesan, Associate Professor of Dermatology, University of California, Irvine, California, USA, commented that cancers develop “not only because they acquire mutations that promote their growth but also because they are able to prevent the immune system from recognising and removing them.” Indeed, prior studies have discovered many mechanisms by which interactions between immune and melanoma cells affect tumour development. For instance, the expression of programmed cell death protein 1 by cancer cells reduces the capability of the immune system’s T cells to attack cancer cells. In this study, the team focussed on mutations in ATR in a mouse model. They introduced mutations to impair the functions of ATR in mice with melanomas and found that tumour growth was accelerated; furthermore, the accumulation of mutations was increased. The authors noted that the mouse melanomas with these ATR mutations “recruited proinflammatory macrophages while repelling T cells important for the anti-tumour response.”

Researchers suggest that their findings demonstrate melanoma cells influence the immune microenvironment inside tumours and thereby facilitate their continued growth. In the future, the team believes that the mouse model used in the study will be of use in further studies to help improve the design of immunotherapies and investigate how melanomas affect immune responses. Summing up the potential of this work, Prof Ganesan explained: “Understanding how developing tumours interact with the immune system to promote their continued growth is a key to developing effective immunotherapies.”

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