Chromium Nanoparticles Improve Macrophage and T Cell Infiltration for Cancer Immunotherapy

Immune checkpoint blockade has been regarded as a highlypromisingcancer immunotherapy approach. However, inefficient immune cell infiltrationand the immunosuppressive tumor microenvironment (TME) remain significantcauses of low clinical response rates. Here, we identified that trivalentchromium irons (Cr3+) could enhance tumor infiltrationof immune cells including M1-type tumor-associated macrophages andCD8(+) T cells. Mechanistically, this effect is dependenton the expression of macrophage inflammatory protein-1 alpha (MIP-1 alpha)and the PI3K/Akt/mTOR pathway. Moreover, the Cr-based nanoparticles(Cr NPs) exhibited superior photothermal properties under near-infraredlaser irradiation, showing great potential in transforming "cold"tumors into "hot" ones. In combination with the PD-1/PD-L1pathway inhibitor, we demonstrated that the Cr NPs significantly improvedanticancer efficacy in mouse models of hepatoma and melanoma by increasingantitumor immune cell infiltration and relieving immunosuppressiveTME. Overall, the Cr NPs offer a new dual-functional platform forlocal and systemic cancer treatments, paving the way toward cancerphotometalloimmunotherapy.