CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)

P1/2, N=53, Not yet recruiting, Shanxi Province Cancer Hospital

P2, N=40, Recruiting, Icahn School of Medicine at Mount Sinai | Not yet recruiting --> Recruiting | Initiation date: Jun 2025 --> Mar 2026

In dMMR EC, the conventional ipilimumab-nivolumab combination yields higher objective response rates (ORR ≈ 63%) than PD-1 monotherapy (ORR ≈ 48%) but is associated with a substantially increased incidence of grade ≥ 3 immune-related adverse events (≈ 23% vs. ≈ 12%)...In contrast, for patients with mismatch repair-proficient (pMMR) tumors, the evidence firmly supports alternative regimens, such as lenvatinib plus pembrolizumab, over dual PD-1/CTLA-4 blockade. Navigating the evolving landscape of immunotherapy in EC requires a nuanced, patient-centric approach. The integration of novel bispecific antibodies may soon simplify the balance between efficacy and toxicity, but until then, treatment selection remains a deliberate process, underscoring the gynecologic oncologist's pivotal role in personalizing care.

See also the graphical abstract(Fig. 1).

High CD44 expression was associated with advanced disease, immune cell infiltration, immune checkpoint gene expression, reduced sensitivity to gemcitabine, paclitaxel, rapamycin, and FMK, and distinct CTLA4/PD-L1 checkpoint profiles. CD44 exhibits compartment-specific regulation in PDAC, linking immune remodeling, exosome signaling, and therapeutic resistance to adverse clinical outcome.

Cadonilimab (AK104) is a first-in-class bispecific antibody targeting programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)...Immune-related AEs occurred in 8 patients (30.8%) in the cadonilimab group and 6 patients (23.1%) in the PD-1 inhibitor group. Compared to PD-1 inhibitor plus chemotherapy, cadonilimab plus chemotherapy significantly improved PFS and OS with a manageable safety profile in the first-line treatment of advanced G/GEJ cancer with PD-L1 CPS <5 in a real-world setting.

This review will attempt to summarize recent discoveries on T-cell functional states in AML and their impact on response to ICIICIs as well as acquired mechanisms of resistance to ICIICIs. Furthermore, strategies to potentially overcome resistance to ICIICIs in the immune-based treatment of AML will be highlighted to provide an outlook for future strategies.

Furthermore, elevated BTF3L4 protein expression was positively associated with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and markedly negatively correlated with CD4+ T cells and CD66b+ neutrophils in HCC tissues. This evidence indicates that BTF3L4 functions as a predictive indicator and is a potential candidate for HCC immunotherapy.

Studying the impact of Treg-derived exosomes on the immune system in cancer is crucial for advancing cancer research and treatment. Understanding these interactions is vital for unraveling the potential implications for cancer development and progression.

Emerging advances in nanomedicine, synthetic biology, and chronotherapy offer additional opportunities to enhance therapeutic specificity and durability, collectively charting a path from mechanistic insight to clinical translation toward realizing the full curative potential of cancer immunotherapy. Trial Registration: ClinicalTrials.gov identifier: LAG-3 (NCT03470922, NCT04082364, NCT05064059, NCT05352672, NCT02614833, NCT03625323, NCT01968109), TIM-3 (NCT03307785, NCT03680508, NCT02608268, NCT02817633), TIGIT (NCT03563716), VISTA (NCT02671955, NCT02812875), IGSF8 (NCT05669430), CD73 (NCT02503774), B7-H3 (NCT02475213, NCT01391143, NCT02628535, NCT03406949, NCT00089245, NCT01099644, NCT01502917), OX40 (NCT01862900, NCT02315066, NCT02410512, NCT02221960, NCT02528357, NCT02923349, NCT02705482), CD27 (NCT02335918, NCT02924038, NCT02302339, NCT02386111, NCT02543645), 4-1BB (NCT01307267, NCT02444793, NCT01471210, NCT02253992, NCT02554812), CD40 (NCT02588443, NCT03329950), ICOS (NCT02904226, NCT02723955, NCT03251924), GITR (NCT02583165, NCT02132754, NCT02697591, NCT03126110, NCT02740270, NCT02598960, NCT01239134, NCT02628574), IDO1 (NCT02752074, NCT02658890, NCT02077881, NCT01560923, NCT02073123, NCT02327078, NCT02178722), TLRs (NCT02556463, NCT02042781), and IL-2-based therapies (NCT02869295, NCT02983045).

Emerging therapeutic strategies aim to disrupt this axis by depleting Tregs (e.g., anti-CD25), blocking MDSC recruitment (e.g., CCR2 inhibitors), or reprogramming TAMs (e.g., CD40 agonists), often in combination with programmed death 1/programmed death-ligand 1 blockade. An integrated approach targeting these populations holds promise for converting pancreatic ductal adenocarcinoma into an immunologically responsive tumor.

Further large-scale, high-quality randomized controlled trials are needed to validate these findings and define the optimal treatment strategy. https://www.crd.york.ac.uk/PROSPERO, identifier CRD420251089855.