TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2)

Early-phase trials combining these approaches in MSS CRC show encouraging activity, while neoadjuvant and adjuvant immunotherapy in MSI-H disease redefines treatment paradigms, with some patients achieving complete responses without surgery. This review synthesizes the current evidence and emerging innovations in CRC immunotherapy and proposes a structured translational framework to extend immunotherapy benefits beyond the MSI-H subset.

Because of the high attrition rate (95%) in the development of drugs for oncology, herding amplifies the loss of human and financial resources incurred during drug development, with large number of patients enrolled in clinical trials of experimental drugs that are unlikely to receive approval for clinical use. Herding concentrates resources at the expense of investment in a broader portfolio of drug development programmes with a spread of risk against attrition.

Compared to clinical combination therapy, RING1 enhanced vascular normalization by 1.8-fold, which subsequently reduced the population of immunosuppressive Tie2-expressing monocytes (TEMs) and elevated the secretion of IFN-γ and granzyme B. Notably, RING1 demonstrated superior tumor-suppressive and anti-metastatic efficacy, as well as improved biosafety, even in orthotopic metastatic models. Overall, RING1 represents a novel therapeutic strategy that remodels the tumor vascular-immune microenvironment with spatiotemporal synchronization via self-assembly, offering a promising alternative to conventional combination therapies.

All together these data show that OCs negatively affect the NK cell cytotoxic activity, allowing the growth of NSCLC CSCs. Our findings reveal a previously unrecognized role of OCs in modulating the immune microenvironment by dampening NK cell function.

Emerging clinical and translational data indicate that disrupting this axis can sensitize MSS-CRC to ICIs: for example, Zanzalintinib combined with Atezolizumab reported survival benefit in the STELLAR-303 trial, and dual blockade of novel checkpoints with PD-(L)1 has been associated with enhanced immune activation in solid tumors. Targeting the MDSC-Treg axis therefore represents a promising strategy to overcome immunotherapy resistance in MSS/pMMR CRC.

More innovative strategies include the use of ICIs in the context of allogeneic haematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy. This review synthesizes current evidence for the use of ICI in different haematological malignancies, and highlights future directions toward biomarker-driven, rationally designed therapeutic combinations.

ILC1 from NV-HCC also displayed enhanced IL-2/IL-15 signaling and interactions with CD8 + T cells via HLA-E, suggestive of potential antitumor crosstalk. While our single-cell cohort size was limited, necessitating validation in larger datasets, our study reveals etiology-associated differences in ILC phenotypes in HCC and provides insight into their potential roles in modulating immune responses within the tumor microenvironment.

We analyzed the T-ALL microenvironment from 40 T-ALL cases treated on the AALL0434 clinical trial and identified a subpopulation of bone-marrow-enriched CCR4+ FOXP3+ T-regulatory cells which express immune checkpoints (PD-1 and TIGIT) and could be targeted with anti-CCR4 therapy. Lastly, we describe the preclinical efficacy of an anti-CCR4 CAR-T in in vitro and in vivo models, paving the way for future translational efforts in chemotherapy refractory T-ALL.

TROPION-Lung10 (NCT06357533) is a phase 3, open-label, multicenter, randomized study evaluating the efficacy and safety of first-line Dato-DXd plus rilvegostomig versus standard-of-care pembrolizumab in patients with advanced/metastatic nonsquamous NSCLC with PD-L1 TC expression ≥50% and without AGAs. TROPION-Lung10 will assess first-line Dato-DXd plus rilvegostomig in patients with advanced/metastatic NSCLC with high PD-L1 expression and without AGAs. ClinicalTrials.gov, identifier NCT06357533.

It reviewed adverse events from novel immunotherapies alone or combined with PD-1/PD-L1/CTLA-4 inhibitors, targeted agents, or chemotherapy. These findings have important clinical implications.

Immune suppression in T2D, and use of metformin, an activator of 5' Adenosine Monophosphate-activated Protein Kinase (AMPK), in such patients, prompted us to examine AMPK regulation of immune checkpoint expression. Chemical inhibition of AMPK with Compound C, and with the pan-BET inhibitor JQ1 or the BRD4-selective PROTAC inhibitor MZ-1, revealed that BET proteins regulate PD-1 and CTLA-4 through an AMPK-dependent pathway and TIM-3 and TIGIT through an AMPK-independent pathway. Personalized approaches to ICB treatment of TNBC patients with comorbid T2D should improve outcomes.

We further report the development of engineered cell membrane vesicles encapsulating Bevacizumab, which are fused with TIGIT-expressing membranes and platelet membranes (referred to as Bev@TPNVs)...The intrahepatic metastasis burden is reduced by approximately 10-fold compared with the control group, and the survival rate of mice within 70 days reaches 50%. This work has the potential to establish a novel standard treatment paradigm that could revolutionize combined immunotherapy following liver metastasis ablation.