High SHP2 expression determines the efficacy of PD‐1/PD‐L1 inhibitors in advanced KRAS mutant non‐small cell lung cancer

Autor: Hui‐Bo Feng, Yu Chen, Zhi Xie, Jie Jiang, Yu‐Min Zhong, Wei‐Bang Guo, Wen‐Qing Yan, Zhi‐Yi Lv, Dan‐Xia Lu, Hong‐Ling Liang, Fang‐Ping Xu, Jin‐Ji Yang, Xue‐Ning Yang, Qing Zhou, Dong‐Kun Zhang, Zhou Zhang, Shao‐Kun Chuai, Heng‐Hui Zhang, Yi‐Long Wu, Xu‐Chao Zhang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Thoracic Cancer, Vol 12, Iss 19, Pp 2564-2573 (2021)
Druh dokumentu: article
ISSN: 1759-7714
1759-7706
DOI: 10.1111/1759-7714.14137
Popis: Abstract Background Src homology region 2 domain‐containing phosphatase 2 (SHP2) is a novel target for Kirsten rat sarcoma oncogene (KRAS) mutant cancer. We retrospectively studied the significance of SHP2 in KRAS mutant non‐small cell lung cancer (NSCLC) treated with immunotherapy and its relationship with tumor microenvironment (TME). Methods Sixty‐one advanced KRAS mutant NSCLC patients who underwent immunotherapy were enrolled. Next‐generation sequencing (NGS) was used to profile mutation status. The expression of SHP2, phospho‐SHP2 (pSHP2), and programmed death ligand 1 (PD‐L1) were analyzed by immunohistochemistry (IHC). Quantitative multiplexed immunofluorescence cytochemistry (mIFC) analysis was conducted to describe the TME. Results SHP2 was heterogeneously expressed in 32 samples in both tumor cells and immune cells and highly expressed (H‐score >10) in 25 (78.1%) samples. The expression levels of SHP2 and pSHP2 were positively correlated. Stromal SHP2 (s‐SHP2) was higher in tumors with PD‐L1 ≥50% versus PD‐L1
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