POU2F1 Induces the Immune Escape in Lung Cancer by Up-regulating PD-L1

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2021 Feb 17

PMID 33594317

Citations 6

Authors

Fei Li

Tianyi Wang

Yinpeng Huang

Affiliations

Soon will be listed here.

Abstract

Purpose: The aim was to research the POU2F1 related genes and mechanism during the progress of immune escape of lung cancer.

Methods: Lung cancer cell lines (H1993, HCC827, A549, H2228, H3122 and H1975) and Human normal lung epithelial cell line (BEAS-2B) were involved in this study. Overexpression or knockdown of POU2F1 was processed in lung cancer cells. POU2F1, PD-L1 and CRK expression in cells were detected by WB and RT-PCR. Flow cytometry and immunofluorescence was used to detect PD-L1 expression on the cell surface. Luciferase reporter detected the promoter activity of CRK. C57BL/6 mice models with knocked down of of POU2F1 were constructed. After tumor formation, anti-PD-1 was administered to detect tumor suppressing ability. IHC assay showed the number of intratumoral CD3+, CD8+, GranzB+ T cells.

Results: POU2F1 and PD-L1 were positively correlated in lung cancer cell lines. Overexpression of POU2F1 promoted the expression level of PD-L1 in lung cancer cells. POU2F1 transcription activated the expression of CRK, and further promoted the expression of PD-L1. Knockdown of POU2F1 promoted the efficacy of Anti-PD-1. In addition, tumor growth ability decreased after POU2F1 was knocked down. Cytotoxic effector cytokines levels, tumor suppressive chemokines and interleukin increased, while IL17a level decreased when POU2F1 was knocked down.

Conclusion: POU2F1 activates the expression of CRK, further promotes the expression of PD-L1, and finally improves the immune escape in lung cancer.

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