{"entity": "researcher", "timestamp": "2026-08-22T06:58:27.496Z", "family": "Mukherjee", "given": "Debayan", "initials": "D", "orcid": "0000-0002-6356-0684", "affiliations": ["Division of Cancer Sciences, The University of Manchester, Manchester M13 9PL, United Kingdom."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/929b4993d0d74179bee23a619fbabfad.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/929b4993d0d74179bee23a619fbabfad"}}, "publications": [{"entity": "publication", "iuid": "eb196eb51acb4d4cbe561c57bf29bad2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/eb196eb51acb4d4cbe561c57bf29bad2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/eb196eb51acb4d4cbe561c57bf29bad2"}}, "title": "Radiotherapy transiently reduces the sensitivity of cancer cells to lymphocyte cytotoxicity.", "authors": [{"family": "Tuomela", "given": "Karoliina", "initials": "K", "orcid": "0000-0003-1631-7435", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87944c4d4b054aeab1c0ba8083840579.json"}}, {"family": "Mukherjee", "given": "Debayan", "initials": "D", "orcid": "0000-0002-6356-0684", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/929b4993d0d74179bee23a619fbabfad.json"}}, {"family": "Ambrose", "given": "Ashley R", "initials": "AR", "orcid": "0000-0002-0639-0690", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9bfffc0c79f94edeb43bbf8569ad0d9e.json"}}, {"family": "Harikrishnan", "given": "Ashish", "initials": "A"}, {"family": "Mole", "given": "Holly", "initials": "H"}, {"family": "Hurlstone", "given": "Adam", "initials": "A", "orcid": "0000-0001-5260-9457", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/414d9ed2674747459ca9f98c0df186ac.json"}}, {"family": "\u00d6nfelt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-5178-7593", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b4b8fcbedb54e2ba38633687f417ae8.json"}}, {"family": "Honeychurch", "given": "Jamie", "initials": "J", "orcid": "0000-0001-6938-0839", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f37e90df4d6d4810932ef9c01ed6b3ac.json"}}, {"family": "Davis", "given": "Daniel M", "initials": "DM", "orcid": "0000-0002-9182-291X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/693c6f441beb4a4e836e534e441ee793.json"}}], "type": "journal article", "published": "2022-01-18", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "119", "issue": "3", "issn-l": "0027-8424"}, "abstract": "The impact of radiotherapy on the interaction between immune cells and cancer cells is important not least because radiotherapy can be used alongside immunotherapy as a cancer treatment. Unexpectedly, we found that X-ray irradiation of cancer cells induced significant resistance to natural killer (NK) cell killing. This was true across a wide variety of cancer-cell types as well as for antibody-dependent cellular cytotoxicity. Resistance appeared 72 h postirradiation and persisted for 2 wk. Resistance could also occur independently of radiotherapy through pharmacologically induced cell-cycle arrest. Crucially, multiple steps in NK-cell engagement, synapse assembly, and activation were unaffected by target cell irradiation. Instead, radiotherapy caused profound resistance to perforin-induced calcium flux and lysis. Resistance also occurred to a structurally similar bacterial toxin, streptolysin O. Radiotherapy did not affect the binding of pore-forming proteins at the cell surface or membrane repair. Rather, irradiation instigated a defect in functional pore formation, consistent with phosphatidylserine-mediated perforin inhibition. In vivo, radiotherapy also led to a significant reduction in NK cell-mediated clearance of cancer cells. Radiotherapy-induced resistance to perforin also constrained chimeric antigen receptor T-cell cytotoxicity. Together, these data establish a treatment-induced resistance to lymphocyte cytotoxicity that is important to consider in the design of radiotherapy-immunotherapy protocols.", "doi": "10.1073/pnas.2111900119", "pmid": "35042775", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8785960"}, {"db": "pii", "key": "2111900119"}], "notes": [], "created": "2026-08-21T12:02:04.190Z", "modified": "2026-08-21T12:02:04.484Z"}]}