2. Academic Validation
  3. Predicting response to immunotherapy in gastric cancer via assessing perineural invasion-mediated inflammation in tumor microenvironment

Predicting response to immunotherapy in gastric cancer via assessing perineural invasion-mediated inflammation in tumor microenvironment

  • J Exp Clin Cancer Res. 2023 Aug 11;42(1):206. doi: 10.1186/s13046-023-02730-0.
Xunjun Li # 1,  Yiyun Wang # 1,  ZhongYa Zhai # 1,  Qingyi Mao 2,  Dianjie Chen 1,  Luxi Xiao 1,  Shuai Xu 1,  Qilin Wu 1,  Keming Chen 1,  Qiantong Hou 1,  Qinglie He 1,  Yuyang Shen 3,  Manchun Yang 1,  Zishan Peng 2,  Siqing He 1,  Xuanhui Zhou 1,  Haoyang Tan 1,  Shengwei Luo 4,  Chuanfa Fang 5,  Guoxin Li 6,  Tao Chen 7 8
Affiliations

Affiliations

  • 1 Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, No. 1838, North Guangzhou Avenue, Guangzhou, 510515, Guangdong Province, China.
  • 2 The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.
  • 3 Medical Image Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.
  • 4 School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.
  • 5 Department of Gastrointestinal and Hernia Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, 341000, Jiangxi, China. [email protected].
  • 6 Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, No. 1838, North Guangzhou Avenue, Guangzhou, 510515, Guangdong Province, China. [email protected].
  • 7 Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, No. 1838, North Guangzhou Avenue, Guangzhou, 510515, Guangdong Province, China. [email protected].
  • 8 Department of Gastrointestinal and Hernia Surgery, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, 341000, Jiangxi, China. [email protected].
  • # Contributed equally.
PMID: 37563649 DOI: 10.1186/s13046-023-02730-0
Abstract

Background: The perineural invasion (PNI)-mediated inflammation of the tumor microenvironment (TME) varies among gastric Cancer (GC) patients and exhibits a close relationship with prognosis and immunotherapy. Assessing the neuroinflammation of TME is important in predicting the response to immunotherapy in GC patients.

Methods: Fifteen independent cohorts were enrolled in this study. An inflammatory score was developed and validated in GC. Based on PNI-related prognostic inflammatory signatures, patients were divided into Clusters A and B using unsupervised clustering. The characteristics of clusters and the potential regulatory mechanism of key genes were verified by RT-PCR, western-blot, immunohistochemistry and immunofluorescence in cell and tumor tissue samples.The neuroinflammation infiltration (NII) scoring system was developed based on principal component analysis (PCA) and visualized in a nomogram together with other clinical characteristics.

Results: Inflammatory scores were higher in GC patients with PNI compared with those without PNI (P < 0.001). NII.clusterB patients with PNI had abundant immune cell infiltration in the TME but worse prognosis compared with patients in the NII.clusterA patients with PNI and non-PNI subgroups. Higher immune checkpoint expression was noted in NII.clusterB-PNI. VCAM1 is a specific signature of NII.clusterB-PNI, which regulates PD-L1 expression by affecting the phosphorylation of STAT3 in GC cells. Patients with PNI and high NII scores may benefit from immunotherapy. Patients with low nomogram scores had a better prognosis than those with high nomogram scores.

Conclusions: Inflammation mediated by PNI is one of the results of tumor-nerve crosstalk, but its impact on the tumor immune microenvironment is complex. Assessing the inflammation features of PNI is a potential method in predicting the response of immunotherapy effectively.

Keywords

Gastric cancer(GC); Inflammatory; Neuroinflammation infiltration(NII) score system; Perinueral invasion(PNI); Tumor microenvironment(TME).

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