Manipulation of TAMs functions to facilitate the immune therapy effects of immune checkpoint antibodies

Bioengineered nanogels for cancer immunotherapy

“…10b). 169 The nanogel decomposition resulted by sensing of the overexpressed MMP-2 after enrichment at the tumour site, and resulted in the release of mannose-modified lipid nanoparticles that targeted tumour macrophages to achieve TAM polarization. Instead, after the released aPD-1 reached the T cells, the PD-1/PD-L1 pathway was blocked and T cells were reactivated, which delayed the growth of melanoma tumours.…”

Engineered Apoptosis-Bioinspired Nanoparticles Initiate Immune Cascade for Cancer Immunotherapy of Malignant Ascites

“…The tumor immune microenvironments (TIME) prompt an intricate cellular communication network of multiple tumor components that inhibit cancer immunity and trigger tumor immune escape. − The adjustment of the immune cell subsets of TIME is helpful to reeducate the TIME components and realize the normalization of immune function. , Under the influence of TIME, tumor-associated macrophages (TAMs) are mainly divided into M1 and M2 subtypes. , Macrophages are the central mediators of immune responses, which can respond to pathogenic or tissue damage signals to initiate the immune cascade reaction by secretion of cytokines or antigen presenting. , Apart from that, the existence of a massive immune infiltration of macrophages in tumor sites differentiating into the M2 phenotype is associated with poor clinical outcome, indicating that the differentiation of macrophages can direct the clinical cancer treatment. , Recently, more researchers, who have focused on the biological mechanism underlying the immune subset activation induced by macrophages, found that repolarizing M2 macrophage to M1 is an effective route by which cancer immunotherapy can be promoted, thereby influencing its clinical outcome. − M2 macrophages are highly correlated with Tim-4 + macrophages. , Bulk RNA sequencing revealed that murine resident peritoneal macrophages are highly expressed Tim-4, which is an essential switch regulating macrophage M1/M2 polarization and intracellular homeostasis. , Given that CD8 + T cells have increased phosphatidylserine (PS) levels following lymph node priming and egress, these effectors are more likely to interact adhesively with Tim-4 + macrophages upon infiltration into serious body cavities . A targetable mechanism of suppression in the serious body cavities is the functional sequestration of cytotoxic T lymphocytes (CTLs) with high PS expression by Tim-4 + macrophages.…”

On-demand integrated nano-engager converting cold tumors to hot via increased DNA damage and dual immune checkpoint inhibition

“…The immune checkpoints act as brakes of the T cells, such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), PD-1 ligand 1 (PD-L1), etc., inhibiting tumor-infiltrating T cells priming and immune activation 27 . Recently, many immune checkpoint inhibitors have been widely used in clinic for tumor therapy 28 , 29 , 30 . However, tumor cells could utilize the co-inhibitory pathways to escape the attack of immune system 31 .…”