Radiotherapy induces resistance to immunotherapy in solid tumours

March 2022 Medical Research Nalinee Pathak

Researchers from UK and Sweden have reported that radiotherapy reduces the sensitivity of tumour cells against immune cell toxicity. Finding from this study were recently published in the journal PNAS.

Radiotherapy is the standard of care in the treatment of many solid tumours. However, it is known that radiation therapy can affect the immune response and consequently the clinical outcomes with immunotherapies. Although the effect of radiation on various immune cells is known, its impact on natural killer (NK) cells is relatively unknown. The team investigated the interaction dynamics between NK cells and irradiated cancer cells using in vitro and in vivo models.

Reduction

The researchers found that irradiated cancers cells were significantly resistant to NK cell killing. This observation was seen across cancer cell types and antibody-dependent cellular toxicity. The resistance to immunotherapy started appearing 72 hours post-radiation and persisted for two weeks. Radiation therapy caused resistance to perforin-induced calcium flux and lysis. Experimental resistance in vivo also showed that radiotherapy causes a significant reduction in NK cell-mediated killing of cancer cells. Also, resistance to perforin constrained chimeric antigen receptor (CAR) T-cell cytotoxicity.

Taken together, the findings of this investigation establish a radiation-induced resistance to lymphocyte toxicity. These observations will have broader implications on developing new therapies, especially combination therapies, including radiation treatment and immunotherapy.

Reference

Tuomela K, Mukherjee D, Ambrose AR, Harikrishnan A, et al. Radiotherapy transiently reduces the sensitivity of cancer cells to lymphocyte cytotoxicity. Proc Natl Acad Sci [Internet]. 2022 Jan 18;119(3):e2111900119.

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