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Role of tumor draining lymph nodes in generation of memory CD8+ T cells in a murine model of colon cancer

Authors :
XIE Shuanglong
ZHA Haoran
YANG Fei
ZHU Bo
LIN Zhihua
Source :
陆军军医大学学报, Vol 45, Iss 7, Pp 645-651 (2023)
Publication Year :
2023
Publisher :
Editorial Office of Journal of Army Medical University, 2023.

Abstract

Objective To investigate the role of tumor draining lymph nodes (TDLN) in the generation of memory CD8+ T cells under the context of neoadjuvant anti-PD-L1 therapy. Methods A mouse transplanted model of CT26/MC38-OVA colon cancer was established to recapitulate clinic neoadjuvant anti-PD-L1 therapy, and then the tumor masses and TDLN were removed in 15 d after transplantation. On day 30 after surgery, the effect of TDLN on the formation of immune memory was assessed under the condition of neoadjuvant PD-L1 antibody therapy by tumor re-challenge. The effect of neoadjuvant PD-L1 on tumor-specific CD8+ T cells was investigated by adoptive transfer CD45.1+ OT-Ⅰ cells. The distribution and phenotype of CD45+ CD8+T cells in various tissues were determined by flow cytometry at the time of surgery (effector phase) and 30 d after surgery (memory phase). Results The tumor mass was reduced significantly after receiving neoadjuvant anti-PD-L1 therapy (P < 0.05). After tumor re-challenge, tumor growth was significantly slowed in the mice treated with neoadjuvant PD-L antibody, whereas TDLN resection accelerated the tumor growth (P < 0.05). However, long-term survival of tumor re-challenge showed that all tumors were eventually subsided, whether or not the mice treated with neoadjuvant PD-L antibody. The results of adoptive reinjection indicated that the number of CD45.1+ CD8+ T cells being stored in TDLN and no-draining lymph nodes (NLN) was the highest (P < 0.05). Tcm (T central memory) cells and Trm (tissue-resident memory) cells were mainly distributed in TDLN and NLN in memory phase (P < 0.05). The distribution and memory phenotype of CD45.1+ CD8+ T cells in TDLN and NLN had no obvous changes after neoadjuvant anti-PD-L1 therapy. Conclusion TDLN is the primary site for the storage of memory CD8+ T cells, but under the condition of neoadjuvant PD-L1 antibody treatment, TDLN resection does not affect their long-term anti-tumor immunity.

Details

Language :
Chinese
ISSN :
20970927
Volume :
45
Issue :
7
Database :
Directory of Open Access Journals
Journal :
陆军军医大学学报
Publication Type :
Academic Journal
Accession number :
edsdoj.398e5c66943c43e2991e25f064a14229
Document Type :
article
Full Text :
https://doi.org/10.16016/j.2097-0927.202301077