Clinically apparent tumors have often established an immunosuppressive tumor microenvironment which renders them "cold," meaning that there are low numbers of immune cells within the tumor. Consequently, novel immunotherapy approaches such as checkpoint inhibitors fail to reactivate the tumor-targeted immune cells. Here we describe the generation of heterotypic tumor-stroma spheroids to study various approaches aiming at the reactivation of cancer immunosurveillance. These spheroids allow to investigate whether a certain immunotherapy or a combination treatment is able to stimulate antitumor immunity in poorly immunological ("cold") tumors, by increasing the number of tumor-infiltrating immune cells ("hot" tumors).
Keywords: ADCC; CAR-T; CXCL12; Cancer immunosurveillance; Checkpoint inhibitor; Immune cell infiltration; PD-1; T cell exclusion; Tumor infiltrating lymphocytes; Tumor-stroma spheroid.