LAG3 elevation

LAG3 demonstrates strong associations within tumor immunity, participating in a range of immune and inflammatory signaling pathways. Elevated levels of LAG3 are linked not only to T cell exhaustion but also to increased immune infiltration and polarization towards M1 macrophages.

We also examined the distribution of LAG3 at the single-cell level and explored its functional significance. A comprehensive and systematic analysis of LAG3 would facilitate a comprehensive evaluation of LAG3 in cancer biology and provide valuable insights for cancer management.

LAG3 expression was correlated with prognosis in multiple cancers, particularly MPM; LAG3 is an independent prognostic biomarker of MPM. LAG3 regulates cancer immunity and is a potential target for ICIs therapy. PD-1 and LAG3 inhibitors may contribute to a better prognosis in MPM.

Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4 T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4 T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment.

Ex vivo biodistribution data revealed increased LAG-3 expression and nanobody uptake in MM-infiltrating organs. Using flow cytometry, a high expression of LAG-3 was observed in MM cells and lymphoid cells, which significantly increased within BM-derived CD8+ T-cells at end-stage of disease. Altogether, these data illustrate increased expression of LAG-3 upon disease progression and fosters the evaluation of LAG-3 blocking therapies, particularly in the context of immunotherapeutic approaches in MM.

Conclusions GBM with high expression of PD1, CTLA4 and LAG3 display frequent mutations in the ERBB-PI3K signaling pathway including EGFR and PTEN. These genes correlated with presence of gamma-delta T cells in tumor infiltrates.

Serum-derived LAG-3 was identified out of a diverse array of chemokine and cytokines as the immune-based factor most significantly associated with improved HGSOC survival. These findings suggest that LAG-3 could be implemented as a non-invasive patient predictive marker for improved HGSOC clinical outcomes.

Our findings suggest that higher levels of LAG3 in UM with histopathologically high-risk parameters predict high metastatic potential and that it could be used as a targeted immunotherapy alone or in combination with PD-1/PD-L1 blockade agents.

Our research showed that iNOS inhibition with the iNOS inhibitor (1400W) and COX2 inhibitor (Celebrex) diminished HCC tumor growth...We also found that iNOS/COX2 blockade result in more CD4+ T helper cells and CD8+ tumor infiltrating lymphocyte (TIL), but reduce the number of exhausted CD4+ T cells and CD8+ T cells (PD1-high, Lag3+, CD39+ Tex). The results suggesting that iNOS/COX2 inhibitor therapy may alleviate HCC growth by promoting a anti-tumorigenic TME, modifying lymphoid spatial localization and gene expression phenotypes and decreasing T-cell exhaustion.

Patients with posttreatment high levels of sLAG3 and LAG3+ cells in PB showed poor prognosis of AGC patients after the nivolumab therapy, suggesting that these are useful predictive biomarkers. LAG3 may be a promising target in immunotherapy for AGC. Clinical trial information: UMIN000032686.

Since the genomic alterations of only BAP1 was associated with the PD-1 therapy response signature and higher LAG3 and VISTA gene expression, it might be a candidate marker for immune checkpoint blockade therapy. Our results on the impact of TSG genotypes on MPM and the correlations between TSG alterations and molecular pathways provide a foundation for developing individualized MPM therapies.

These checkpoints thus represent attractive therapeutic targets, and indeed the LAG3 inhibitor relatlimab was recently approved for the treatment of metastatic melanoma in combination with anti-PD-1 therapy...We further saw that the prognostic value of LAG3 levels varies depending on the tissue site queried (i.e., primary tumor versus metastases), and that relatively higher LAG3 levels at metastatic sites may predict a better response to immunotherapy and longer overall survival after the development of metastatic disease. These findings may have important implications for the design of future studies involving LAG3 or other immunotherapies in RCC.