TY  - JOUR
AU  - Griessinger, Christoph M
AU  - Schmid, Andreas M
AU  - Sonanini, Dominik
AU  - Schörg, Barbara F
AU  - Jarboui, Mohamed Ali
AU  - Bukala, Daniel
AU  - Mucha, Natalie
AU  - Fehrenbacher, Birgit
AU  - Steinhilber, Julia
AU  - Martella, Manuela
AU  - Kohlhofer, Ursula
AU  - Schaller, Martin
AU  - Zender, Lars
AU  - Rammensee, Hans-Georg
AU  - Quintanilla-Martinez, Leticia
AU  - Röcken, Martin
AU  - Kneilling, Manfred
AU  - Pichler, Bernd J
TI  - The administration route of tumor-antigen-specific T-helper cells differentially modulates the tumor microenvironment and senescence.
JO  - Carcinogenesis
VL  - 40
IS  - 2
SN  - 1460-2180
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2019-01745
SP  - 289 - 302
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30753335
DO  - DOI:10.1093/carcin/bgy161
UR  - https://inrepo02.dkfz.de/record/144225
ER  -