Abstract
Increasing evidence has clarified that the tumor microenvironment (TME) is closely related to the prognosis and therapeutic efficacy of cancer. However, there is no reliable TME evaluation system used to accurately predict the prognosis of and therapeutic efficacy in gastric cancer. We evaluated the immune microenvironment score (IMS) of 1422 gastric cancer samples based on 51 immune cell signatures. We explored the relationship between the IMS and prognosis, immune cell infiltration, cancer subtype, and potential immune escape mechanisms. The results show that activation of the stroma and decreased levels of immune infiltration were associated with a low IMS. A high IMS was characterized by Epstein–Barr virus infection, increased mutation load, microsatellite instability, and immune cell infiltration. A high IMS was also related to high expression of immune checkpoint molecules (PD-1/PD-L1). Finally, patients with a high IMS had a better response to PD-1/PD-L1 inhibitors and may be more suitable for immune checkpoint inhibitors (area under the curve = 0.81). In addition, a low IMS may be converted into the immune-infiltrating subtype after romidepsin treatment. Stratification based on the IMS may enable gastric cancer patients to benefit more from immunotherapy and help identify new cancer treatment strategies.
Highlights
Gastric cancer is the fifth most common malignant tumor and the fourth leading cause of cancer death[1]
We focused on evaluating tumor microenvironment (TME) characteristics to in the The Cancer Genome Atlas (TCGA) cohort, the immune microenvironment score (IMS) showed the study the immune activity, prognosis, and immunotherapy highest expression in stage I disease, there was no significant response in gastric cancer
The results showed that the CD8 cells in the high IMS group significantly infiltrated the middle of the tumor tissue compared with the low IMS group (Fig. 6a), which is consistent with the transcriptome results we analyzed
Summary
Gastric cancer is the fifth most common malignant tumor and the fourth leading cause of cancer death[1]. Its morbidity and mortality have declined in the past few years, gastric cancer is still a serious global health problem[2,3,4]. Surgery, chemotherapy, radiation therapy, and targeted therapy are the main treatment methods for gastric cancer[5]. Committee on Cancer (AJCC) staging system and histological classification are the most important tools for the stratification, classification, and treatment of patients with gastric cancer[6,7]. High heterogeneity has been found in gastric cancer, and new stratifications have been proposed for gastric cancer[8]. It is necessary to identify other important factors to stratify patients more precisely with gastric cancer to better guide clinical treatment and improve prognosis
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