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.
- 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.
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.