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Qualitative analysi...
Qualitative analysis of tumor-infiltrating lymphocytes across human tumor types reveals a higher proportion of bystander CD8+ T cells in non-melanoma cancers compared to melanoma
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- Gokuldass, Aishwarya (författare)
- Copenhagen University Hospital
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- Draghi, Arianna (författare)
- Copenhagen University Hospital
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- Papp, Krisztian (författare)
- Eötvös Loránd University
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- Borch, Troels Holz (författare)
- Copenhagen University Hospital
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- Nielsen, Morten (författare)
- Copenhagen University Hospital
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- Westergaard, Marie Christine Wulff (författare)
- Copenhagen University Hospital
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- Andersen, Rikke (författare)
- Copenhagen University Hospital
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- Schina, Aimilia (författare)
- Copenhagen University Hospital
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- Bol, Kalijn Fredrike (författare)
- Copenhagen University Hospital
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- Chamberlain, Christopher Aled (författare)
- Copenhagen University Hospital
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- Presti, Mario (författare)
- Copenhagen University Hospital
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- Met, Özcan (författare)
- Copenhagen University Hospital,University of Copenhagen
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- Harbst, Katja (författare)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Lauss, Martin (författare)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Soraggi, Samuele (författare)
- Aarhus University
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- Csabai, Istvan (författare)
- Eötvös Loránd University
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- Szállási, Zoltán (författare)
- Danish Cancer Society
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- Jönsson, Göran (författare)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Svane, Inge Marie (författare)
- Copenhagen University Hospital
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- Donia, Marco (författare)
- Copenhagen University Hospital
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(creator_code:org_t)
- 2020-11-12
- 2020
- Engelska 15 s.
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://www.mdpi.com...
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Background: Human intratumoral T cell infiltrates can be defined by quantitative or qualitative features, such as their ability to recognize autologous tumor antigens. In this study, we reproduced the tumor-T cell interactions of individual patients to determine and compared the qualitative characteristics of intratumoral T cell infiltrates across multiple tumor types. Methods: We employed 187 pairs of unselected tumor-infiltrating lymphocytes (TILs) and autologous tumor cells from patients with melanoma, renal-, ovarian-cancer or sarcoma, and single-cell RNA sequencing data from a pooled cohort of 93 patients with melanoma or epithelial cancers. Measures of TIL quality including the proportion of tumor-reactive CD8+ and CD4+ TILs, and TIL response polyfunctionality were determined. Results: Tumor-specific CD8+ and CD4+ TIL responses were detected in over half of the patients in vitro, and greater CD8+ TIL responses were observed in melanoma, regardless of previous anti-PD-1 treatment, compared to renal cancer, ovarian cancer and sarcoma. The proportion of tumor-reactive CD4+ TILs was on average lower and the differences less pronounced across tumor types. Overall, the proportion of tumor-reactive TILs in vitro was remarkably low, implying a high fraction of TILs to be bystanders, and highly variable within the same tumor type. In situ analyses, based on eight single-cell RNA-sequencing datasets encompassing melanoma and five epithelial cancers types, corroborated the results obtained in vitro. Strikingly, no strong correlation between the proportion of CD8+ and CD4+ tumor-reactive TILs was detected, suggesting the accumulation of these responses in the tumor microenvironment to follow non-overlapping biological pathways. Additionally, no strong correlation between TIL responses and tumor mutational burden (TMB) in melanoma was observed, indicating that TMB was not a major driving force of response. No substantial differences in polyfunctionality across tumor types were observed. Conclusions: These analyses shed light on the functional features defining the quality of TIL infiltrates in cancer. A significant proportion of TILs across tumor types, especially non-melanoma, are bystander T cells. These results highlight the need to develop strategies focused on the tumor-reactive TIL subpopulation.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Immunotherapy
- Tumor microenvironment
- Tumor-infiltrating lymphocytes
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
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Cancers
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Till lärosätets databas
- Av författaren/redakt...
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Gokuldass, Aishw ...
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Draghi, Arianna
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Papp, Krisztian
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Borch, Troels Ho ...
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Nielsen, Morten
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Westergaard, Mar ...
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visa fler...
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Andersen, Rikke
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Schina, Aimilia
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Bol, Kalijn Fred ...
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Chamberlain, Chr ...
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Presti, Mario
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Met, Özcan
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Harbst, Katja
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Lauss, Martin
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Soraggi, Samuele
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Csabai, Istvan
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Szállási, Zoltán
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Jönsson, Göran
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Svane, Inge Mari ...
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Donia, Marco
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Cancers
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Lunds universitet