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Open Access 01-12-2021 | NSCLC | Original Article

CD38 identifies pre-activated CD8+ T cells which can be reinvigorated by anti-PD-1 blockade in human lung cancer

Authors: Pin Wu, Lufeng Zhao, Yongyuan Chen, Zhongwei Xin, Mingjie Lin, Zhixing Hao, Xiaoke Chen, Di Chen, Dang Wu, Ying Chai

Published in: Cancer Immunology, Immunotherapy | Issue 12/2021

Abstract

Background

CD38 has been observed expressing in activated T cells, while the features and functions of CD38+ T cells in human NSCLC are still unclear.

Methods

Here we uncovered the correlation between CD38 expression and survival and immune infiltration levels in tumor of NSCLC. Then, we collected samples from 51 NSCLC patients to study the biological feature and response to anti-PD-1 of tumor-infiltrating CD38+ CD8+ T cells in vitro.

Results

We found CD38 expression correlated with the survival and immune infiltration levels of NSCLC. It is interesting that CD38+ CD8+ T cells enriched in the tumors expressed higher level of cytotoxic molecule, cytokines and PD-1 than CD38− CD8+ T cells. Moreover, PD-1+ subset in tumor-infiltrating CD38+ CD8+ T cells expressed higher level of activated markers than PD-1+ CD38− CD8+ T cells. Next, we found tumor-infiltrating CD38+ CD8+ T cells expressed higher level of CD103, IFN-γ, TNF-α and perforin than CD38− CD8+ T cells when were reactivated in vitro. Finally, we observed that CD38+ CD8+ T cells isolated from tumors could be reinvigorated by anti-PD-1 in vitro.

Conclusions

Our findings demonstrate that CD38 expression defines a subset of CD8+ T cells enriched in tumors of NSCLC which have paradoxical phenotypes and response to anti-PD-1. Our results suggest a pre-priming of these cells is may exist in tumor and consequentially facilitate it acquiring both anti-tumor potency and exhausted phenotype which can be reinvigorated by PD-1 blockade.

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Title: CD38 identifies pre-activated CD8+ T cells which can be reinvigorated by anti-PD-1 blockade in human lung cancer
Authors: Pin Wu
Lufeng Zhao
Yongyuan Chen
Zhongwei Xin
Mingjie Lin
Zhixing Hao
Xiaoke Chen
Di Chen
Dang Wu
Ying Chai
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
NSCLC
Published in: Cancer Immunology, Immunotherapy / Issue 12/2021
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-02949-w

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Abstract

Background

Methods

Results

Conclusions

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