ACAP1, short for Arfgap with Coil-coil, Ankryin repeat, and PH domain I, is an Arf6 GTPase-activating protein (GAP) that plays a crucial role in endocytic recycling [3,4,5,6]. It is involved in sorting cargoes at the recycling endosome for their return to the plasma membrane by recognizing recycling sorting signals, which is essential for normal cellular function [4,6]. It has also been associated with pathways related to cell migration and G protein-coupled receptor trafficking [2,3,5].

In solid tumors, ACAP1 deficiency predicts inferior immunotherapy response. ACAP1 is highly expressed in immune-related tissues and cells, especially in tumor-infiltrating lymphocytes (TILs). Its expression is negatively regulated by promoter DNA methylation, and SPI1 positively regulates its expression in immune cells. ACAP1 levels positively correlate with TIL infiltrating levels, especially CD8+ T cells. Functionally, depletion of ACAP1 by RNA interference significantly impairs T cell-mediated killing of tumor cells, indicating its importance for normal TIL function [1]. In ovarian cancer, high ACAP1 expression predicts poor prognosis, and its expression and methylation status are strongly correlated with immune infiltration levels, immunomodulators, and chemokines [3]. In lung adenocarcinoma, low ACAP1 expression is correlated with unsatisfactory overall and disease-specific survival, and overexpression of ACAP1 attenuates cell proliferation, migration, and invasion while promoting apoptosis [5].

In conclusion, ACAP1 is essential for endocytic recycling and normal TIL function. Its deficiency is associated with poor prognosis and immunotherapy response in multiple cancer types. The study of ACAP1 through functional studies, especially those related to its deficiency, helps to understand its role in tumor immunity and provides potential biomarkers for cancer prognosis and immunotherapy response prediction.