Journal Article

DKFZ-2019-01745

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The administration route of tumor-antigen-specific T-helper cells differentially modulates the tumor microenvironment and senescence.

Griessinger, C. M. ; Schmid, A. M. ; Sonanini, D. ; Schörg, B. F. ; Jarboui, M. A. ; Bukala, D. ; Mucha, N. ; Fehrenbacher, B. ; Steinhilber, J. ; Martella, M. ; Kohlhofer, U. ; Schaller, M. ; Zender, L.DKFZ* ; Rammensee, H.-G.DKFZ* ; Quintanilla-Martinez, L. ; Röcken, M. ; Kneilling, M. ; Pichler, B. J.

2019
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/carcin/bgy161

Abstract: 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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Contributing Institute(s):

1. Translationale Gastrointestinale Onkologie (V076)
2. DKTK Tübingen (L801)

Research Program(s):

1. 319H - Addenda (POF3-319H) (POF3-319H)

Appears in the scientific report 2019

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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