Fig. 5

Myeloid immune cells regulate T-cell infiltration. (Figure created with BioRender.com). M1-like tumor-associated macrophages (TAMs) express high levels of CXCL9,10,11 and 12 and recruit stem cell-like CD8⁺ or CD8A⁺ tissue-resident T cells via the CXCL9-CXCR3 axis. CD169 macrophages promote tumor microenvironment reprogramming by recruiting CD8⁺ T/NK cells and inhibiting the accumulation of myeloid-derived suppressor cells (MDSCs)/regulatory T cells (Tregs). M1-like TAMs also highly express MHC-II, CD68 markers, and CD80 and CD86 co-stimulatory molecules, promoting the recruitment of T cells through local tumor antigen presentation. M2-like TAMs, expressing high levels of DC-SIGN, may promote Treg accumulation and suppress T-cell infiltration by directly engaging in the expression and secretion of multiple anti-inflammatory cytokines, and inhibit T cells activity via the PD-L1/PD-1 pathway. They may also downregulate the CXCL12-CXCR3 and CXCL12-CXCR4 axes to suppress T cells infiltration, upregulate CD86-CTLA4 to inhibit T cells activity, and possibly block CD8⁺ T-cell infiltration via GRN-TNFRSF1A interaction or LAIR1. MDSCs can mediate CD8⁺ T cell incompetence via the PD-L1/PD-1 pathway, and express OPN proteins to interact with PD-1⁺ T cells infiltrating the tumor, promoting tumor immune escape. Dendritic cells can express CCL22, CCL17, CCL19, and IL-32, recruiting naive T cells; they also induce T cell inactivation and apoptosis by increasing FOXP3 expression through high levels of IDO1 expression. Natural killer (NK) cells stimulate BDCA3⁺ dendritic cells by producing FLT3LG, increasing T-cell infiltration, but they also inhibit the anti-tumor effect of T cells by expressing the KLRB1 gene (encoding CD161)