LGALS9 (Galectin 9)

Conditional gal9 knockout in DCs led to enhanced tumor growth in vivo, underscoring a role for gal9 in T cell-dependent antitumor immunity. Collectively, this study reports gal9-mediated HLA-DR organization at the DC synapse, uncovering a mechanism through which intracellular galectins coordinate immune receptor positioning to enhance CD4+ T cell activation.

Gal-9 increased IL-1β level as a critical inflammatory cytokine in the proliferation and resistance of AML cells to therapy. According to this finding, targeting and blocking the TIM-3/Gal-9 autocrine loop can suppress IL-Ιβ production and facilitate AML treatment.

Immune profiling shows P2 as immunosuppressive, characterized by LGALS9 and M2 macrophages. Our proteogenomic analyses provide a molecular landscape of LMS, revealing biological insights, patient outcome stratification, and therapeutic targets.

Patients with GC/GEJ with increased sTIM-3 and sGal-9 levels had a significantly reduced overall survival with a hazard ratio of 1.77 (sTIM-3 high), 1.82 (sGal-9 high), and 2.27 (sTIM-3 high+sGal-9 high), respectively. Collectively, sTIM-3 and sGal-9 may serve as novel non-invasive biomarkers for diagnosis and outcome prediction in patients with GC/GEJ.

Furthermore, therapeutic delivery of Galunisertib using choline-modified lipid nanoparticles synergizes with αPD-1, fostering the conversion of exhausted CD8⁺ T cells into responsive Ly108⁺CX3CR1⁺ subsets and suppressing liver metastases. Collectively, our results identify hepatocyte TGFβ signaling as a targetable checkpoint against liver metastases.

Our findings reveal that high expression of LGALS9 suppresses T cell function, fosters a strongly immunosuppressive tumor microenvironment, and is associated with chemotherapy resistance, ineffective immunotherapy, and poor prognosis. LGALS9 may serve as a biomarker for predicting immunotherapy response. This knowledge has the potential to facilitate early diagnosis, precise molecular typing, accurate prognosis evaluation, and the development of personalized treatment strategies that can overcome tumor drug resistance and improve patient outcomes.

IL-27 may enhance immunosuppressive mechanisms in CLL by modulating immune checkpoint expression, potentially contributing to disease progression. These ex vivo findings in PBMCs from CLL patients indicate the IL-27-associated modulation of checkpoint expression under the conditions tested. In the absence of parallel healthy-donor controls, CLL specificity cannot be established in this study.

Moreover, higher levels of LGALS9 in LN tissue are associated with poor overall survival of melanoma patients (p= 0.0018). In summary, this study reveals an altered landscape of sEV proteome in the afferent lymphatic fluid of melanoma, highlighting distinct sEV proteins that are uniquely present in the SLN during PMN development.

Our findings demonstrated that MFSD12 upregulation in LIHC strongly correlates with poor prognosis. This association was potentially attributed to MFSD12's dual roles: promoting tumor cell proliferation, migration, and metastasis while critically modulating the tumor immune microenvironment, particularly through interaction with the HAVCR2/LGALS9 immune checkpoint axis.

The microRNA miR-491-5p regulated T cell-mediated immunity by targeting and inhibiting LGALS9, which was similar to the effect of LGALS9 knockout. Overall, the key target LGALS9 and its inhibitor miR-491-5p represent promising potential for treating gastric cancer.

In contrast, a much larger number of soluble markers was needed to distinguish CRC patients from HVs among the middle-aged. Collectively, these findings underscore the relevance of observing age stratification for biomarker discovery and lay the groundwork for further exploration of soluble immune mediators in ageing related to tumour pathophysiology.

Our study identifies a Galectin-9/BTK/STAT3 axis that drives macrophage-mediated immune suppression in LN metastases, offering a potential therapeutic strategy.