Brain tumor immunotherapies often fail because immune cells are slowed down by immunosuppressive conditions in the tumor. Cytotoxic T cells are immune cells that ultimately induce tumor cell death. These cytotoxic T cells do migrate into brain tumors - but rapidly lose their functionality due to the immunosuppressive conditions.
In this study, it was found that in brain tumors, a specific type of immune cells that migrate from the blood to the tumor site, myeloid cells, are necessary for the sustained function of cytotoxic T cells.
If the myeloid cells lack certain surface proteins, the MHCII molecules, cytotoxic T cells remain inactive. However, if the so-called osteopontin level decreases due to MHCII-mediated activation of myeloid cells, cytotoxic T cells regain their functionality.
Michael Kilian, Ron Sheinin, Chin Leng Tan, Mirco Friedrich, Christopher Krämer, Ayelet Kaminitz, Khwab Sanghvi, Katharina Lindner, Yu-Chan Chih, Frederik Cichon, Benjamin Richter, Stefanie Jung, Kristine Jähne, Miriam Ratliff, Robert M Prins, Nima Etminan, Andreas von Deimling, Wolfgang Wick, Asaf Madi, Lukas Bunse, Michael Platten
Cancer Cell. 2023 Feb 13;41(2):235-251.e9.
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