Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China.
*These authors contributed equally to this work.
#These authors jointly supervised this work.
Background: Targeting emerging T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT)/CD155 axis shows promise for restoring anti-tumor immunity, but its immune phenotypes and prognostic significance in a large cohort of pancreatic ductal adenocarcinoma (PDAC) are limited.
Methods: Three seven-color multispectral panels were rationally designed to investigate the protein expression, immune-microenvironmental feature, prognostic value, and the response to adjuvant chemotherapy of TIGIT/CD155 in 272 PDAC specimens using multiplex immunohistochemistry.
Results: We revealed low immunogenicity and high heterogeneity of the PDAC immune microenvironment featured by abundant CD3+ T cells and CD68+ macrophages and low infiltration of activated cytotoxic T lymphocytes. TIGIT and CD155 were highly expressed in PDAC tissues compared to paracancerous tissues. Tumor-infiltrating lymphocytes expressing TIGIT were correlated with high densities of CD45RO+ T cells; TIGTI+CD8+ T cells were associated with high infiltration of CD3+CD45RO+FOXP3+. CD155+CK+ were significantly related to high densities of CD3+ and CD3+CD8+CD45RO+ T cells. High positive rates for TIGIT in TCs, CD8+ T cells, and CD155 in macrophages were correlated with poor progression-free and disease-specific survival, respectively, and their clinical significance was correlated with PD-L1 status. Notably, spatial co-existence of TIGIT+CK+ or TIGIT+CD8+ and CD155+CD68+ indicated poor survival and resistance to adjuvant chemotherapy response in patients with PDAC.
Conclusion: Our findings suggest that targeting TIGIT/CD155 immunosuppressive axis may guide patient stratification and improve the clinical outcome of PDAC.
Keywords: Pancreatic ductal adenocarcinoma, TIGIT/CD155, PD-L1, adjuvant chemotherapy, multiplex immunohistochemistry