The following summary is “Neoadjuvant Chemotherapy Is Associated with Altered Immune Cell Infiltration and an Anti-Tumorigenic Microenvironment in Resected Pancreatic Cancer” published in the December 2022 issue of Oncology by Costa et al.
The effect of neoadjuvant chemotherapy on the tumor immune milieu is little understood, despite its growing use in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC). Researchers used quantitative, spatially resolved multiplex immunofluorescence and digital image analysis to identify T-cell subpopulations, macrophage polarization states, and myeloid cell subpopulations in a multi-institutional cohort of primary tumors resected at diagnosis (n=299) and in a comparative set of tumors resected following FOLFIRINOX-based neoadjuvant therapy (n=36) or primary surgery (n=30).
Associations between the immunological microenvironment and patient outcomes were assessed using multivariate-adjusted Cox proportional hazards models. Immune cells in patients’ tumors in the multi-institutional resection cohort showed significant heterogeneity. These cells were most frequently seen in the stroma. Utilizing immune cell densities, unsupervised clustering revealed four distinct configurations of infiltrating immune cells. 20% of tumors showed a pattern associated with better patient survival, which was defined by an abundance of T cells (T cell-rich) and a lack of immunosuppressive granulocytes and macrophages.
A larger CD8:CD4 ratio, a higher M1:M2-polarized macrophage ratio, and a lower CD15+ ARG1+ immunosuppressive granulocyte density were all related with neoadjuvant treatment. 72 % of tumors exposed to neoadjuvant exhibited a T cell-rich pattern with low levels of immunosuppressive granulocytes and macrophages. Colocalization of M1-polarized macrophages and tumor cells was related with increased tumor pathologic response and better patient survival following neoadjuvant treatment. Patients with pancreatic ductal adenocarcinoma (PDAC) who undergo neoadjuvant chemotherapy with FOLFIRINOX experience an anti-tumorigenic change in their immune microenvironment.