Bone marrow expands the repertoire of functional T cells targeting tumor-associated antigens in patients with resectable non-small-cell lung cancer

Seyer Safi, Yoshikane Yamauchi, Slava Stamova, Anchana Rathinasamy, Jan op den Winkel, Simone Jünger, Mariana Bucur, Ludmilla Umansky, Arne Warth, Esther Herpel, Martin Eichhorn, Hauke Winter, Hans Hoffmann, Philipp Beckhove

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The efficacy of cancer immunotherapy may be improved by increasing the number of circulating tumor-reactive T cells. The bone marrow is a priming site and reservoir for such T cells. The characteristics of bone marrow-derived tumor-reactive T cells are poorly understood in patients with non-small-cell lung cancer (NSCLC). To compare the responsiveness of tumor antigen-reactive T cells from the bone marrow with matched peripheral blood samples in patients with resectable NSCLC, we used flow cytometry, cytokine capture assays and enzyme-linked immunospot assays to examine the responsiveness of T cells to 14 tumor antigens in matched bone marrow and peripheral blood samples from patients with resectable NSCLC or benign tumors and tumor-free patients. T cells with reactivity to tumor antigens were detected in the bone marrow of 20 of 39 (51%) NSCLC patients. The panel of tumor antigens recognized by bone marrow-derived T cells was distinct from that recognized by peripheral blood-derived T cells in NSCLC patients. Unlike for peripheral blood T cells, the presence of tumor-reactive T cells in the bone marrow did not correlate with recurrence-free survival after curative intent resection of NSCLC. T cells with reactivity to tumor antigens are common in the bone marrow of patients with NSCLC. Tumor-reactive T cells of the bone marrow have the potential to significantly broaden the total repertoire of tumor-reactive T cells in the body. To clarify the role of tumor-reactive T cells of the bone marrow in T cell-based immunotherapy approaches, clinical studies are needed (ClinicalTrials.gov: NCT02515760).

Original languageEnglish
Article numbere1671762
JournalOncoImmunology
Volume8
Issue number12
DOIs
StatePublished - 2 Dec 2019
Externally publishedYes

Keywords

  • Lung cancer
  • T cells
  • bone marrow
  • immunotherapy

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