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Chemotherapy markedly reduces B cells but not T cells and NK cells in patients with cancer

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Abstract

Chemotherapy is still the backbone of systemic treatment in the majority of cancers. However, immunotherapies, especially those based on checkpoint inhibition, are additional therapy options for many. For this, functional T cells are a mandatory requirement. The aim of this prospective study was to investigate the influence of chemotherapy on the cellular immune status of individual patients. Peripheral blood samples of 26 patients with solid malignancies undergoing chemotherapy were analyzed for lymphocyte populations and their subsets in a longitudinal approach. Chemotherapy decreased total B lymphocyte counts [median value (25–75 percentile): before chemotherapy 76/µl (39–160) vs. after chemotherapy 49/µl (24–106); p = 0.001]. Among B cells, specific subsets decreased particularly [naïve B cells (49/µl (21–111) vs. 25/µl (13–56); p = 0.001], memory B cells [3/µl (2–8) vs. 2/µl (1–4); p = 0.001], and class-switched B cells [11/µl (6–20) vs. 6/µl (3–12); p = 0.011]. In contrast, chemotherapy had no influence on the total numbers of CD4 + and CD8 + T lymphocytes or on their subsets (T helper cells 1, 2, and 17 as well as cytotoxic T cells in early, intermediate, late, terminal effector and exhausted status as well as both T-cell types with naïve, center memory, effector memory, activated, or regulatory phenotype). Furthermore, the count of natural killer (NK) lymphocytes showed no significant change before and after chemotherapy. In summary, this study shows a decrease of B lymphocytes during systemic chemotherapy, but no relevant effect on T lymphocytes, NK lymphocytes and their subsets. This could support the idea of an effective additive T-cell-dependent immunotherapy to chemotherapy.

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Abbreviations

CD:

Cluster of differentiation

CR:

Complete remission

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

ECD:

Phycoerythrin texas red-X

EDTA:

Ethylenediaminetetraacetic acid

FITC:

Fluoreszeinisothiocyanat

FOLFIRI:

Folinic acid, fluorouracil, irinotecan

FOLFIRINOX:

Folinic acid, fluorouracil, irinotecan, oxaliplatin

G-CSF:

Granulocyte-colony stimulating factor

ICD:

Immunogenic cell death

NSCLC:

Non-small cell lung cancer

PC:

Phycoerythrin–cyanin

PD:

Progressive disease

PD-1:

Programmed cell death protein 1

PE:

Phycoerythrin

PR:

Partial remission

SCLC:

Small cell lung cancer

SD:

Stable disease

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Acknowledgements

We would like to thank Gernot Müller, Professor for computational statistics and data analysis, University of Augsburg, for his statistical support, Prof. Bruno Märkl, director of the Institute of Pathology and Molecular Diagnostics, University Medical Center Augsburg, for his help with data interpretation, and Mrs. Tatajana Lensjaka on behalf of all laboratory staff for the technical support in our laboratory.

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Authors and Affiliations

  1. Department of Hematology and Oncology, University Medical Center Augsburg, Stenglinstr.2, 86156, Augsburg, Germany

    Johanna Waidhauser, Anja Schuh, Martin Trepel, Ann-Kristin Schmälter & Andreas Rank

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  1. Johanna Waidhauser
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  2. Anja Schuh
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  3. Martin Trepel
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  4. Ann-Kristin Schmälter
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  5. Andreas Rank
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Contributions

JW: study design, data acquisition and interpretation, and manuscript drafting. AS: data acquisition and interpretation. MT: manuscript drafting. A-KS: manuscript drafting. AR: study design, data acquisition, and interpretation, manuscript drafting

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Correspondence to Johanna Waidhauser.

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The authors declare that they have no conflict of interest.

Ethical approval and ethical standards

The study was approved by the local medical ethical committee (institutional review board, reference number BKF 2016/09) and written informed consent was obtained. All procedures involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Patients and healthy blood donors consented to the use of their blood samples and data for research and publications.

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Waidhauser, J., Schuh, A., Trepel, M. et al. Chemotherapy markedly reduces B cells but not T cells and NK cells in patients with cancer. Cancer Immunol Immunother 69, 147–157 (2020). https://doi.org/10.1007/s00262-019-02449-y

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  • DOI: https://doi.org/10.1007/s00262-019-02449-y

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