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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1504220

High density of TCF1+ stem-like tumor-infiltrating lymphocytes is associated with favorable disease-specific survival in NSCLC Authors and affiliations

Provisionally accepted
Dagny Førde Dagny Førde 1*Thomas Kilvær Thomas Kilvær 1,2Mona Irene Pedersen Mona Irene Pedersen 1Egil Støre Blix Egil Støre Blix 1,2Ilona Urbarova Ilona Urbarova 1Erna-Elise Paulsen Erna-Elise Paulsen 1,2Mehrdad Rakaee Mehrdad Rakaee 1,2,3Lill-Tove Rasmussen Busund Lill-Tove Rasmussen Busund 1,2Tom Donnem Tom Donnem 1,2Sigve Andersen Sigve Andersen 1,2
  • 1 UiT The Arctic University of Norway, Tromsø, Norway
  • 2 University Hospital of North Norway, Tromsø, Troms, Norway
  • 3 Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway

The final, formatted version of the article will be published soon.

    Tumor-infiltrating lymphocytes are both prognostic and predictive biomarkers for immunotherapy response. However, less is known about the survival benefits of their subpopulations. Using machine learning models, we assessed the clinical association of the CD8+, PD1+, TCF1+ cell subset by multiplex immunohistochemistry using tissue microarrays in 553 non-small cell lung cancer (NSCLC) patients and its correlation with other immune cell biomarkers. We observed positive correlations between TCF1 and CD20 (r=0.37), CD3 (r=0.45) and CD4 (r=0.33). Notably, triple positive (CD8+PD1+TCF1+) were rare, only observed in 29 of 553 patients (5%). Our analysis revealed that cells co-expressing TCF1 with either CD8+ or PD1+ were independent prognostic markers of diseasespecific survival in multivariable analysis (HR=0.728, p=0.029 for CD8+TCF1+, and HR=0.612, p=0.002 for PD1+TCF1+). To pilot the subtype of abundant CD8-TCF1+ cells, we explored an immune cell infiltrated whole slide-image and found the majority to be CD4+. Overall, these findings suggest that assessment of CD8+, PD1+, TCF1+ could serve as a potential prognostic biomarker in NSCLC.

    Keywords: NSCLC, digital pathology, CD8, PD1, TCF1, machine learning

    Received: 30 Sep 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Førde, Kilvær, Pedersen, Blix, Urbarova, Paulsen, Rakaee, Busund, Donnem and Andersen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Dagny Førde, UiT The Arctic University of Norway, Tromsø, Norway

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.