| 게재년월 |
2021/10 |
| 논문제목 |
Dysregulation of TFH-B-TRM lymphocyte cooperation is associated with unfavorable anti-PD-1 responses in EGFR-mutant lung cancer
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| 참여교수 |
이인석
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| 학술지명 |
NATURE COMMUNICATIONS |
| 초록 |
Patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations exhibit an unfavorable response to PD-1 inhibitor through unclear mechanisms. Hypothesizing that EGFR mutations alter tumor-immune interactions, we compare tumor-infiltrating lymphocytes between EGFR mutant (EGFR-MT) and wild type (EGFR-WT) tumors through single-cell transcriptomic analysis. We find that B cells, CXCL13-producing follicular helper CD4+ T (TFH)-like cells, and tissue-resident memory CD8+ T (TRM)-like cells decreased in EGFR-MT tumors. The NOTCH-RBPJ regulatory network, which is vital for persistence of TRM state, is perturbed, and the interactions between TFH and B cells through the CXCL13-CXCR5 axis disappear in EGFR-MT tumors. Notably, the proportion of TRM-like cells is predictive for anti-PD-1 response in NSCLC. Our findings suggest that the impairment of TFH-B-TRM cooperation in tertiary lymphoid structure formation, accompanied by the dysregulation of TRM homeostasis and the loss of TFH-B crosstalk, underlies unfavorable anti-PD-1 response in EGFR-MT lung tumors. |
| 게재정보 |
Nat Commun. 2021 Oct 18;12(1):6068 |
| 총저자명 |
Jae-Won Cho, Seyeon Park, Gamin Kim, Heonjong Han, Hyo Sup Shim, Sunhye Shin, Yong-Soo Bae, Seong Yong Park, Sang-Jun Ha, Insuk Lee, Hye Ryun Kim
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