Nanohydroxyapatite Stimulates PD-L1 Expression to Boost Melanoma Combination Immunotherapy.

Abstract

Although checkpoint-inhibitor immunotherapy held tremendous advances, improving immune response during treatment has always been an urgent clinical issue. With the help of mRNA microarray technology, it was found that short rod-like nanohydroxyapatite (nHA) promoted the upregulation of CD274 and PD-L1 related gene transcription, which was confirmed by the significantly enhanced PD-L1 expression level in B16, B16F10, and 4T1 cells in vitro. Hence, an injectable in situ responsive hydrogel reservoir embed with nHA and PD-1/PD-L1 inhibitor was engineered for a combination immunotherapy by peritumoral administration. The results confirmed that the combinational strategy effectively suppressed tumorigenesis and tumor growth, recovered the abnormal lactate dehydrogenase, aspartate transaminase, and alanine aminotransferase indicators, and significantly elongated the life span of a tumor-bearing mouse. The substantive progress mainly derived from nHA-induced T cell infiltration reinforcement in a tumor site and CD8+ T cell polarization in spleen, implying that nHA might function as an immunomodulator for melanoma immunotherapy.