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Within the tumour microenvironment, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2009cells undergo full effector differentiation and acquire cytotoxic anti-tumour functions in specialized niches\n                    <jats:sup>3\u20137<\/jats:sup>\n                    . Although interactions with type\u20091 conventional dendritic cells have been implicated in this process\n                    <jats:sup>3\u20135,8\u201310<\/jats:sup>\n                    , the underlying cellular players and molecular mechanisms remain incompletely understood. Here we show that inflammatory monocytes can adopt a pivotal role in intratumoral T\u2009cell stimulation. These cells express\n                    <jats:italic>Cxcl9<\/jats:italic>\n                    ,\n                    <jats:italic>Cxcl10<\/jats:italic>\n                    and\n                    <jats:italic>Il15<\/jats:italic>\n                    , but in contrast to type\u20091 conventional dendritic cells, which cross-present antigens, inflammatory monocytes obtain and present peptide\u2013major histocompatibility complex class\u2009I complexes from tumour cells through \u2018cross-dressing\u2019. Hyperactivation of MAPK signalling in cancer cells hampers this process by coordinately blunting the production of type\u2009I interferon (IFN-I) cytokines and inducing the secretion of prostaglandin\u2009E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ), which impairs the inflammatory monocyte state and intratumoral T\u2009cell stimulation. Enhancing IFN-I cytokine production and blocking PGE\n                    <jats:sub>2<\/jats:sub>\n                    secretion restores this process and re-sensitizes tumours to T\u2009cell-mediated immunity. Together, our work uncovers a central role of inflammatory monocytes in intratumoral T\u2009cell stimulation, elucidates how oncogenic signalling disrupts T\u2009cell responses through counter-regulation of PGE\n                    <jats:sub>2<\/jats:sub>\n                    and IFN-I, and proposes rational combination therapies to enhance immunotherapies.\n                  <\/jats:p>","DOI":"10.1038\/s41586-024-08257-4","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T11:03:39Z","timestamp":1732705419000},"page":"716-725","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":170,"title":["Cancer cells impair monocyte-mediated T cell stimulation to evade 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J.Z. is a founder and scientific advisor of Quantro Therapeutics. G.C. has received grants from Celgene, Boehringer-Ingelheim, Roche, BMS, Iovance Therapeutics, and Kite Pharma. The institution that G.C. is affiliated with has received fees for his participation on an advisory board or for presentation at a company-sponsored symposium from Genentech, Roche, BMS, AstraZeneca, NextCure, Geneos Tx, and Sanofi\/Avensis. G.C. has patents in the domain of antibodies and vaccines targeting the tumour vasculature, as well as technologies related to T\u2009cell expansion and engineering for T\u2009cell therapy. G.C. has received royalties from the University of Pennsylvania regarding CAR T\u2009cell technology. G.C. is a named inventor on patent applications filed by the Ludwig Institute for Cancer Research pertaining to the subject matter disclosed herein. D.D.L. has received a grant from Hoffmann-La Roche. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}