TY - JOUR
T1 - hnRNPA2B1 potentiates the immune escape of non-small cell lung cancer by accelerating tumor microenvironment acidification
AU - Wei, Yiqun
AU - Li, Weijie
AU - Wu, Runmiao
AU - Cao, Yanfei
AU - Yang, Shuanying
N1 - Publisher Copyright:
© 2025 Elsevier Inc.
PY - 2025/9
Y1 - 2025/9
N2 - The role of lactate on tumorigenesis is definitely not just a metabolic waste, but could mainly regulate tumorigenesis and tumor microenvironment, including immune escape. Here, this study was performed to investigate the role of N6-methyladenosine (m6A) reader hnRNPA2B1 on non-small cell lung cancer (NSCLC) lactate metabolism and immune escape. Elevated hnRNPA2B1 was found in NSCLC samples and correlated with the poor clinical survival rate. Functionally, results unveiled that hnRNPA2B1 accelerated the acidification of tumor microenvironment, thereby promoting the immune escape of NSCLC from PBMC's killing effect. Moreover, additional lactate administration could reduce the cytotoxicity and cytokines secretion of activated PBMCs, and hnRNPA2B1 knockdown could reverse this phenomenon. Mechanistically, hnRNPA2B1 targeted MCT4 to enhance its mRNA stability by m6A-dependent type. hnRNPA2B1 promoted MCT4 stability to trigger the lactate-mediated acidification microenvironment and immune escape. Overall, this research focused on investigating the role of hnRNPA2B1 in the NSCLC microenvironment acidity and the lactate-mediated immune escape, which might provide a potential target to reverse the resistance to tumor immunotherapy.
AB - The role of lactate on tumorigenesis is definitely not just a metabolic waste, but could mainly regulate tumorigenesis and tumor microenvironment, including immune escape. Here, this study was performed to investigate the role of N6-methyladenosine (m6A) reader hnRNPA2B1 on non-small cell lung cancer (NSCLC) lactate metabolism and immune escape. Elevated hnRNPA2B1 was found in NSCLC samples and correlated with the poor clinical survival rate. Functionally, results unveiled that hnRNPA2B1 accelerated the acidification of tumor microenvironment, thereby promoting the immune escape of NSCLC from PBMC's killing effect. Moreover, additional lactate administration could reduce the cytotoxicity and cytokines secretion of activated PBMCs, and hnRNPA2B1 knockdown could reverse this phenomenon. Mechanistically, hnRNPA2B1 targeted MCT4 to enhance its mRNA stability by m6A-dependent type. hnRNPA2B1 promoted MCT4 stability to trigger the lactate-mediated acidification microenvironment and immune escape. Overall, this research focused on investigating the role of hnRNPA2B1 in the NSCLC microenvironment acidity and the lactate-mediated immune escape, which might provide a potential target to reverse the resistance to tumor immunotherapy.
KW - Immune escape
KW - Lactate
KW - MCT4
KW - Non-small cell lung cancer
KW - hnRNPA2B1
UR - https://www.scopus.com/pages/publications/105006938454
U2 - 10.1016/j.freeradbiomed.2025.05.395
DO - 10.1016/j.freeradbiomed.2025.05.395
M3 - 文章
C2 - 40379155
AN - SCOPUS:105006938454
SN - 0891-5849
VL - 237
SP - 52
EP - 64
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -
