Figure 4.

Strategies overcoming resistance to PD-1/PDL1 by promoting T-cell infiltration (A), reversing T cell exhaustion (B), and CD8+ T cell stimulation (C). (A) methods promoting T-cell infiltration include targeted therapy, vascular-normalization therapies, CAR T therapy and low-dose radiotherapy; (B) treatment options to reinvigorate of T cell exhaustion include blocking the alternative immune checkpoints, targeting co-stimulatory receptors, inhibiting soluble immune suppressive mediators and epigenetically coordinating exhausted CD8+ T (Tex) cells. (C) strategies targeting immune-suppressive cells in TME such as TAM, Treg and CAF to stimulate T cells. In addition, radiotherapy and microbiota-centered interventions also reprogram the immunosuppressive TME, promoting antitumor T-cell responses. The picture was created with BioRender.com. CAR, chimeric antigen receptor, Treg, regulatory T lymphocytes; DC, dendritic cell; TAM, tumor associated macrophages; CAF, cancer associated fibroblasts; MARCO, macrophage receptor with collagenous structure; HRH1, histamine and histamine receptor H1.