SIGLEC10 (Sialic Acid Binding Ig Like Lectin 10)

Mechanistically, PU.1 directly targeted Siglec-10, a key immune checkpoint of macrophage. Our study highlights the pro-tumorigenic role of PU.1 in macrophages and provides experimental evidence regarding the mechanism of the PU.1-Siglec10 axis in modulating immune checkpoint activity within the glioma microenvironment.

Hypothesizing that similar mechanisms in a tumor microenvironment may attenuate anti-tumor immunity, we observed that expression of SIGLEC10, the human homolog of Siglecg, was associated with resistance to anti-PD1 therapy in human melanomas. In conclusion, B cell expression of FcγRIIB and Siglec-G appear to play an essential role in maintaining transplant tolerance and in tumor evasion of anti-tumor immunity.

Siglecs are key immunomodulators that mediate cell-cell and pathogen interactions, playing pivotal roles in human diseases. Further research into their mechanisms and clinical applications is essential to fully harness their therapeutic potential. Targeting Siglecs offers promising avenues for developing novel immunotherapies, particularly in cancer and autoimmune diseases.

Future research will focus on preparing hMacTrigger by constructing vectors encoding TNF-α under the control of each identified gene promoter and evaluating its anti-tumor effects and side effects in vivo. This study represents a critical step toward the clinical application of the MacTrigger strategy and advances its potential use in cancer immunotherapy.

Based on this model, Vorinostat was prioritized as a candidate therapeutic agent, and subsequent validation confirmed its significant inhibitory effects on the glioma microenvironment. These findings elucidate the molecular mechanisms of GAMs in glioma, uncover the immunological landscape of the tumor microenvironment, and identify potential therapeutic targets and drug action mechanisms.

Our results suggest that high Siglec-G/10 expression aggravates the immune suppressive tumor microenvironment and impedes the immunotherapy efficacy in HNSCC, which indicates that targeting Siglec-G/10 may represent a promising therapeutic option for improving the immunotherapy efficacy in HNSCC.

Tumor cornification greatly impacts immune infiltration, and the LICC scheme may guide clinical medication of anti-PD-1+chemo treatment in patients with LUSC.

SIM@TR-NP-mediated sonodynamic immunotherapy exhibited potent antitumor efficacy in ovarian cancer and exhibited substantial potential for improving the immunosuppressive TME. This study presents an emerging therapeutic regimen for ovarian cancer that synergizes TAM-based antitumor immunotherapy and SDT.

This inhibition of innate immune responses such as phagocytosis provides a mechanistic explanation for the ability of CHI3L1 to stimulate ICPs and inhibit adaptive immune responses in cancer and diseases such as COPD. The ability of CHI3L1 to simultaneously inhibit innate immune responses, stimulate ICPs, inhibit T cell costimulation, and regulate a number of other oncogenic and inflammation pathways suggests that CHI3L1-targeted therapeutics are promising interventions in cancer, COPD, and other disorders.

Therefore, this strategy can have significant potential in the prevention of tumor metastases and recurrence. To the best of our understanding, this study represents a pioneering showcase of tumor pyroptosis, induced by glycolytic inhibitors, which can be effectively coordinated with DIP-mediated TAM polarization for immune activation, offering a new paradigm for differentially sustained drug delivery to foster cancer immunotherapy.

Furthermore, we examine the synergy between CD24 and Siglec-10 in shaping the immunosuppressive tumour microenvironment and discuss the implications for combination therapies. Therefore, understanding the roles of CD24 and Siglec-10 in cancer immunotherapy opens exciting possibilities for the development of novel therapeutics.

Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.