Perspectives for immunotherapy ofEBV‐associatedGLELC: A relatively “hot” tumor microenvironment

Abstract

BackgroundEpstein–Barr virus (EBV)‐associated gastric lymphoepithelioma‐like carcinoma (EBVaGLELC) represents a small number of gastric cancer (GC), and research on tumor microenvironment (TME) and treatment strategy are still lacking.AimsHere, we aim to elucidate the immune features of this rare disease and further help to develop more effective treatment options.Materials & MethodsA retrospective analysis was conducted between 2019 to 2022 in West China Hospital to reveal the immunological characteristics of EBV‐positive GLELC. The difference of immune cell subset and tumor vascular structure between gastric denocarcinoma (GAC) and EBVaGLELC will be pointed out.Discussion13 patients with GELEC and 8 patients with GAC were retrospectively studied. The heterogeneity of the immune cell profile was then confirmed through multiplexed immunofluorescence staining (mIF), which revealed a higher proportion of CD3+ T cells, CD8+ T cells, and Treg cells in the EBV‐associated GLELC group. Such a distinct TME may provide therapeutic advantages, and patients with this rare subtype of GC could be good candidates for immune checkpoint inhibitors (ICIs). Angiogenesis in EBV‐positive GLELC may be less intense than that in gastric adenocarcinoma (GAC), a feature that might decrease their susceptibility to antiangiogenic therapy. Furthermore, we reported a 52‐year‐old male with advanced EBV‐positive GLELC who showed a favorable response to the combined therapy with . A repeat evaluation showed sustained partial response (PR), and the progression‐free survival (PFS) was more than 34 months until now.ConclusionCompared with GAC, EBVaGLELC revealed higher T cell infiltration and less intense of angiogenesis. It displays relatively “hot” TME that may provide the rationality to treat with immunotherapy in EBV‐related GLELC.

Efficacy of immune checkpoint inhibitors differs in various status of carcinoma: a study based on 29 cohorts with 3255 participants

“…Recently, increasing evidences highlighted the importance of viral infection in influencing the efficacy of immunotherapy. Pre-clinical and clinical evidences have recognized that the viral infection may play a crucial role in boosting the immune response and improve prognosis of cancer patients undergoing ICIs treatment [ 11 – 14 ]. To the best of our knowledge, this study was firstly investigated the impact of viral infection on outcomes of cancer patients treated with ICIs based on a comprehensive survey (29 cohorts incorporating 3,255 individuals), multiple viruses types (EBV, HBV, HCV, and HPV) and multiple tumor types (including GC, NPC, HCC and HNSCC).…”

“…Upregulation of PD-1 and its ligands PD-L1 were observed during acute viral infection and after infection with persistent viruses including important human pathogens such as HBV, HCV, and EBV [ 23 – 26 ]. Moreover, viral infection associated carcinomas were typically characterized by abundant immune cell infiltration [ 11 , 12 ], which might further positively affect the efficacy of ICIs.…”

“…In contrast, the immune-inflamed phenotype, referred to as "hot tumors", exhibited a significantly stronger response to ICIs [ 8 , 10 ]. Studies demonstrated that tumors associated viral infection often exhibit an “hot tumor” [ 11 , 12 ]. However, the impact of viral infection in tumors on the efficacy of ICIs remains a topic of debate in clinical practice, with no established consensus.…”