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

Safi, Seyer and Yamauchi, Yoshikane and Stamova, Slava and Rathinasamy, Anchana and Op den Winkel, Jan and Juenger, Simone and Bucur, Mariana and Umansky, Ludmilla and Warth, Arne and Herpel, Esther and Eichhorn, Martin and Winter, Hauke and Hoffmann, Hans and Beckhove, Philipp (2019) Bone marrow expands the repertoire of functional T cells targeting tumor-associated antigens in patients with resectable non-small-cell lung cancer. ONCOIMMUNOLOGY, 8 (12). ISSN 2162-402X,

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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).

Item Type: Article
Uncontrolled Keywords: COLORECTAL-CANCER; THERAPY; CD8(+); IMMUNOTHERAPY; LYMPHOCYTES; STATISTICS; RESERVOIR; SURVIVAL; SUBSETS; SITE; Lung cancer; bone marrow; T cells; immunotherapy
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 25 Mar 2020 08:23
Last Modified: 25 Mar 2020 08:23
URI: https://pred.uni-regensburg.de/id/eprint/25974

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