Prognostic implications of immune classification in a multicentre cohort of patients with small intestinal adenocarcinoma

Abstract

The diagnosis of small intestinal adenocarcinoma (SIAC) is usually determined at an advanced stage due to non-specific symptoms and the difficulty of exploring the small intestine. Therefore, the majority of SIAC patients have limited chemotherapeutic options. Until recently, the development of novel and effective therapies for SIAC have been limited owing to the low number of samples that have been collected and the low incidence of SIAC. Immunotherapies are becoming a focus. However, in SIAC, only a few studies to identify immunotherapy-responsive subgroups and their prognostic indicators have been reported. In the present study, we categorise primary SIAC into four types of tumour immune microenvironments and propose a strategy for identifying patient subgroups that are most likely to be immunotherapy-responsive. Formalin-fixed, paraffin-embedded tissue samples of a multicentre cohort of patients with SIAC (n=195) were collected using tissue microarrays. Immunohistochemical (IHC) stains for PD-L1, PD-1, and CD8 were performed, and microsatellite instability was evaluated using an IHC stain. Tumour microenvironment immune type (TMIT) I [PD-L1-positive tumour cells and CD8-high tumour-infiltrating lymphocytes (TILs)] and TMIT III (PD-L1-positive tumour cells and CD8-low TILs) show the best and worse prognoses, respectively. PD-L1 expression was significantly associated with high microsatellite instability (MSI) status. CD8-high TILs were positively correlated with PD-1-high TILs and high MSI. The TMIT I subgroup demonstrated a more patent CD8/PD-L1/PD-1 signalling pathway compared to other TMITs. Therefore, the TMIT I subgroup can be expected to have an effective response to immune checkpoint inhibitor therapies in SIAC. Such classification of SIACs into four immune types can be useful in predicting the prognosis of patients and the identification of immunotherapy-responsive subgroups.

Keywords: CD8; PD-L1; small intestinal adenocarcinoma; tumour microenvironment immune type.