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000144225 0247_ $$2doi$$a10.1093/carcin/bgy161
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000144225 1001_ $$aGriessinger, Christoph M$$b0
000144225 245__ $$aThe administration route of tumor-antigen-specific T-helper cells differentially modulates the tumor microenvironment and senescence.
000144225 260__ $$aOxford$$bOxford Univ. Press$$c2019
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000144225 520__ $$aCancer treatment with adoptively transferred tumor-associated antigen-specific CD4+ T-helper cells is a promising immunotherapeutic approach. In the pancreatic cancer model RIP-Tag2, the intraperitoneal (i.p.) application of Tag-specific TH1 cells exhibited a profound antitumoral efficiency. We investigated, whether an intravenous (i.v.) application of Tag-TH1 cells induces an equivalent therapeutic effect. Adoptively transferred fluorescent Tag-TH1 cells revealed a pronounced homing to the tumors after either i.p. or i.v. transfer, and both routes induced an almost equivalent therapeutic effect as demonstrated by magnetic resonance imaging, blood glucose level course and histology. The i.v. administration of Tag-TH1 cells induced p16INK4-positive/Ki67-negative tumor senescence more efficiently than i.p. administration. Both routes replenish host CD4+ T cells by transferred T cells and recruitment of B and dendritic cells to the tumors while reducing CD8+ T cells and depleting macrophages. Both administration routes efficiently induced a similar antitumoral efficiency despite the pronounced senescence induction after i.v. administration. Thus, a combinatory i.v./i.p. injection of therapeutic cells might overcome limitations of the individual routes and improve therapeutic efficacy in solid tumors.
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000144225 7001_ $$aSchmid, Andreas M$$b1
000144225 7001_ $$aSonanini, Dominik$$b2
000144225 7001_ $$aSchörg, Barbara F$$b3
000144225 7001_ $$aJarboui, Mohamed Ali$$b4
000144225 7001_ $$aBukala, Daniel$$b5
000144225 7001_ $$aMucha, Natalie$$b6
000144225 7001_ $$aFehrenbacher, Birgit$$b7
000144225 7001_ $$aSteinhilber, Julia$$b8
000144225 7001_ $$aMartella, Manuela$$b9
000144225 7001_ $$aKohlhofer, Ursula$$b10
000144225 7001_ $$aSchaller, Martin$$b11
000144225 7001_ $$0P:(DE-He78)1ba2900406378e069d32db376c7818db$$aZender, Lars$$b12$$udkfz
000144225 7001_ $$0P:(DE-He78)58a4f09f3edfdce451d520a5be7979fc$$aRammensee, Hans-Georg$$b13$$udkfz
000144225 7001_ $$aQuintanilla-Martinez, Leticia$$b14
000144225 7001_ $$aRöcken, Martin$$b15
000144225 7001_ $$aKneilling, Manfred$$b16
000144225 7001_ $$aPichler, Bernd J$$b17
000144225 773__ $$0PERI:(DE-600)1474206-8$$a10.1093/carcin/bgy161$$gVol. 40, no. 2, p. 289 - 302$$n2$$p289 - 302$$tCarcinogenesis$$v40$$x1460-2180$$y2019
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