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Sökning: WFRF:(Lövgren G.) > (2020) > The Outcome of Ex V...

The Outcome of Ex Vivo TIL Expansion Is Highly Influenced by Spatial Heterogeneity of the Tumor T-Cell Repertoire and Differences in Intrinsic In Vitro Growth Capacity between T-Cell Clones

Poschke, Isabel C. (författare)
Heidelberg Univ Hosp, Dept Gen Surg, Heidelberg, Germany.;German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany.;German Canc Res Ctr, DKTK Immune Monitoring Unit, Neuenheimer Feld 460, D-69120 Heidelberg, Germany.
Hassel, Jessica C. (författare)
Heidelberg Univ Hosp, Dept Dermatol, Heidelberg, Germany.;Heidelberg Univ Hosp, Natl Ctr Tumor Dis, Heidelberg, Germany.
Rodriguez-Ehrenfried, Aaron (författare)
Heidelberg Univ Hosp, Dept Gen Surg, Heidelberg, Germany.;German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany.
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Lindner, Katharina A. M. (författare)
Heidelberg Univ Hosp, Dept Gen Surg, Heidelberg, Germany.;German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany.;German Canc Res Ctr, Clin Cooperat Unit Neuroimmunol & Brain Tumor Imm, Heidelberg, Germany.
Heras-Murillo, Ignacio (författare)
Heidelberg Univ Hosp, Dept Gen Surg, Heidelberg, Germany.;German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany.;Ctr Nacl Invest Cardiovasc CNIC, Immunol Lab, Madrid, Spain.
Appel, Lena M. (författare)
Heidelberg Univ, Div Theoret Syst Biol, German Canc Res Ctr, Heidelberg, Germany.;Heidelberg Univ, BioQuant Ctr, Heidelberg, Germany.;Tech Univ Munich TUM, Inst Med Microbiol Immunol & Hyg, Munich, Germany.
Lehmann, Johanna (författare)
Heidelberg Univ Hosp, Dept Gen Surg, Heidelberg, Germany.;German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany.
Lövgren, Tanja (författare)
Karolinska Institutet,Uppsala universitet,Institutionen för medicinska vetenskaper,Klinisk immunologi,Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
Wickstrom, Stina L. (författare)
Karolinska Institutet
Lauenstein, Claudia (författare)
Heidelberg Univ Hosp, Dept Gen Surg, Heidelberg, Germany.;German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany.
Roth, Jasmin (författare)
Heidelberg Univ Hosp, Dept Dermatol, Heidelberg, Germany.;Heidelberg Univ Hosp, Natl Ctr Tumor Dis, Heidelberg, Germany.
Koenig, Anna-Katharina (författare)
Heidelberg Univ Hosp, Dept Gen Surg, Heidelberg, Germany.
Haanen, John B. A. G. (författare)
Netherlands Canc Inst, Dept Mol Oncol & Immunol, Amsterdam, Netherlands.
van den Berg, Joost (författare)
Netherlands Canc Inst, Dept Mol Oncol & Immunol, Amsterdam, Netherlands.
Kiessling, Rolf (författare)
Karolinska Institutet
Bergmann, Frank (författare)
Heidelberg Univ Hosp, Dept Pathol, Heidelberg, Germany.
Flossdorf, Michael (författare)
Heidelberg Univ, Div Theoret Syst Biol, German Canc Res Ctr, Heidelberg, Germany.;Heidelberg Univ, BioQuant Ctr, Heidelberg, Germany.;Tech Univ Munich TUM, Inst Med Microbiol Immunol & Hyg, Munich, Germany.
Strobel, Oliver (författare)
German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany.
Offringa, Rienk (författare)
Heidelberg Univ Hosp, Dept Gen Surg, Heidelberg, Germany.;German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany.
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Heidelberg Univ Hosp, Dept Gen Surg, Heidelberg, Germany;German Canc Res Ctr, Div Mol Oncol Gastrointestinal Tumors, Heidelberg, Germany.;German Canc Res Ctr, DKTK Immune Monitoring Unit, Neuenheimer Feld 460, D-69120 Heidelberg, Germany. Heidelberg Univ Hosp, Dept Dermatol, Heidelberg, Germany.;Heidelberg Univ Hosp, Natl Ctr Tumor Dis, Heidelberg, Germany. (creator_code:org_t)
AMER ASSOC CANCER RESEARCH, 2020
2020
Engelska.
Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 26:16, s. 4289-4301
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Purpose: During our efforts to develop tumor-infiltrating lymphocyte (TIL) therapy to counter the devastating recurrence rate in patients with primary resectable pancreatic ductal adenocarcinoma (PDA), we found that PDA TILs can readily be expanded in vitro and that the majority of resulting TIL cultures show reactivity against the autologous tumor. However, the fraction of tumor-reactive T cells is low. We investigated to which extent this was related to the in vitro expansion. Experimental Design: We compared the clonal composition of TIL preparations before and after in vitro expansion using T-cell receptor (TCR) deep sequencing. Our findings for PDA were benchmarked to experiments with melanoma TILs. Results: We found that the TIL TCR repertoire changes dramatically during in vitro expansion, leading to loss of tumor-dominant T-cell clones and overgrowth by newly emerging T-cell clones that are barely detectable in the tumor. These changes are primarily driven by differences in the intrinsic in vitro expansion capacity of T-cell clones. Single-cell experiments showed an association between poor proliferative capacity and expression of markers related to antigen experience and dysfunction. Furthermore, we found that spatial heterogeneity of the TIL repertoire resulted in TCR repertoires that are greatly divergent between TIL cultures derived from distant tumor samples of the same patient. Conclusions: Culture-induced changes in clonal composition are likely to affect tumor reactivity of TIL preparations. TCR deep sequencing provides important insights into the factors that govern the outcome of in vitro TIL expansion and thereby a path toward optimization of the production of TIL preparations with high therapeutic efficacy.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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