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Publication : The administration route of tumor-antigen-specific T-helper cells differentially modulates the tumor microenvironment and senescence.

First Author  Griessinger CM Year  2019
Journal  Carcinogenesis Volume  40
Issue  2 Pages  289-302
PubMed ID  30753335 Mgi Jnum  J:274224
Mgi Id  MGI:6295335 Doi  10.1093/carcin/bgy161
Citation  Griessinger CM, et al. (2019) The administration route of tumor-antigen-specific T-helper cells differentially modulates the tumor microenvironment and senescence. Carcinogenesis 40(2):289-302
abstractText  Cancer treatment with adoptively transferred tumor-associated antigen-specific CD4+ T-helper cells is a promising immunotherapeutic approach. In the pancreatic cancer model RIP-Tag2, the intraperitoneal (i.p.) application of Tag-specific TH1 cells exhibited a profound antitumoral efficiency. We investigated, whether an intravenous (i.v.) application of Tag-TH1 cells induces an equivalent therapeutic effect. Adoptively transferred fluorescent Tag-TH1 cells revealed a pronounced homing to the tumors after either i.p. or i.v. transfer, and both routes induced an almost equivalent therapeutic effect as demonstrated by magnetic resonance imaging, blood glucose level course and histology. The i.v. administration of Tag-TH1 cells induced p16INK4-positive/Ki67-negative tumor senescence more efficiently than i.p. administration. Both routes replenish host CD4+ T cells by transferred T cells and recruitment of B and dendritic cells to the tumors while reducing CD8+ T cells and depleting macrophages. Both administration routes efficiently induced a similar antitumoral efficiency despite the pronounced senescence induction after i.v. administration. Thus, a combinatory i.v./i.p. injection of therapeutic cells might overcome limitations of the individual routes and improve therapeutic efficacy in solid tumors.
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