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The administration route of tumor-antigen-specific T-helper cells differentially modulates the tumor microenvironment and senescence.
- Source :
- Carcinogenesis; Feb2019, Vol. 40 Issue 2, p289-302, 14p
- Publication Year :
- 2019
-
Abstract
- Cancer treatment with adoptively transferred tumor-associated antigen-specific CD4<superscript>+</superscript> T-helper cells is a promising immunotherapeutic approach. In the pancreatic cancer model RIP-Tag2, the intraperitoneal (i.p.) application of Tag-specific T<subscript>H</subscript>1 cells exhibited a profound antitumoral efficiency. We investigated, whether an intravenous (i.v.) application of Tag-T<subscript>H</subscript>1 cells induces an equivalent therapeutic effect. Adoptively transferred fluorescent Tag-T<subscript>H</subscript>1 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-T<subscript>H</subscript>1 cells induced p16<superscript>INK4</superscript>-positive/Ki67-negative tumor senescence more efficiently than i.p. administration. Both routes replenish host CD4<superscript>+</superscript> T cells by transferred T cells and recruitment of B and dendritic cells to the tumors while reducing CD8<superscript>+</superscript> 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- DRUG administration
TUMOR microenvironment
B cell lymphoma
OLD age
CANCER treatment
Subjects
Details
- Language :
- English
- ISSN :
- 01433334
- Volume :
- 40
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 136179906
- Full Text :
- https://doi.org/10.1093/carcin/bgy161