Fig. 3 |. Eosinophils as biomarkers and accessory cells in cancer immunotherapy.

a, CAR T cell treatment resulted in intratumoral infiltration of eosinophils. Depletion of eosinophils caused downregulation of CXCL9 and CXCL10, suggesting that tumor-infiltrating eosinophils actively recruit CAR T cells. b, Therapeutic inhibition of DPP4 in mice using sitagliptin results in induction of IL-33, increased CCL11 and subsequent eosinophil infiltration, degranulation, secretion of the eosinophil cationic proteins MBP (major basic protein), ECP (eosinophil cationic protein) and EDN (eosinophil-derived neurotoxin), and cytotoxicity, which leads to reduced tumor growth. c, Treatment by immune checkpoint blockade, such as with anti-CTLA4, anti-PD-L1 and/or anti-PD-1 is associated with increased eosinophilia that is concomitant with better prognosis. Mechanistically, anti-CTLA4 therapy results in CD4⁺ and CD8⁺ T cell-dependent accumulation of eosinophils into the TME via T cell-expressing CCL11 and CCL5. IFN-γ production by eosinophils is essential for anti-CTLA4 treatment-induced vessel normalization. Blockade of PD-1 results in increased secretion of GM-CSF by ILC2s expressing PD-1, which leads to eosinophil survival and increased eosinophil-mediated cytotoxicity and antitumor immunity. Pink boxes indicate direct eosinophil-derived mediators and/or activities; blue boxes indicate indirect eosinophil-mediated lymphocyte activities.