This review analyzes the current landscape of existing randomized clinical trials, highlighting the efficacy of immune checkpoint inhibitors (ICIs) like pembrolizumab, avelumab, and dostarlimab. These findings underscore the importance of tailoring treatments based on the molecular characteristics of each tumor and paving the way for future advancements in the field of gynecologic oncology. Despite promising results, this article acknowledges the necessity of further research to refine patient selection criteria and explore combination strategies that can overcome resistance mechanisms.

Key to immunotherapy efficacy in EC is the tumor's mismatch repair status, with MMR-deficient tumors demonstrating a higher tumor mutational burden and increased PD-L1 expression, making them more susceptible to immune checkpoint inhibitors (ICIs) such as pembrolizumab, durvalumab, and dostarlimab. To overcome resistance in cold tumors, novel therapies, including Chimeric Antigen Receptor (CAR) T cells and tumor-infiltrating lymphocytes are being explored, offering targeted immune-based strategies to enhance treatment efficacy. This review discusses the current understanding of immunotherapy in EC, emphasizing the prognostic and therapeutic implications of MMR status, TME composition, and emerging cell-based therapies.

Elevated baseline lactate dehydrogenase was linked to shorter PFS. SHR-1701 combined with XELOX and bevacizumab demonstrated a manageable safety profile and potent antitumor activity in unresectable mCRC.

This study demonstrated the potential of a multifaceted therapeutic approach targeting TAMs to enhance anti-tumor immune responses in breast cancer.

Atirizumab, duvalizumab, atezolizumab, and serplulimab can significantly improve the clinical outcomes of SCLC. Finally, we clarified that the emerging trend of low-dose radiotherapy help overcome the inhibitory signals that limit T-cell infiltration in the tumor matrix. In summary, considering the rapid development of this field, these combined therapy strategies may have unlimited potential to further improve the efficacy of radiotherapy combined with immunotherapy for patients.

P2, N=60, Recruiting, Hoffmann-La Roche | Trial completion date: Feb 2025 --> Sep 2025 | Trial primary completion date: Feb 2025 --> Sep 2025

P2, N=80, Active, not recruiting, AIO-Studien-gGmbH | Recruiting --> Active, not recruiting | Trial completion date: Nov 2026 --> Apr 2027 | Trial primary completion date: Nov 2026 --> Apr 2027

P1/2, N=48, Recruiting, University Health Network, Toronto | Not yet recruiting --> Recruiting

P1, N=48, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

P2, N=3, Active, not recruiting, Liza Villaruz, MD | Recruiting --> Active, not recruiting | N=35 --> 3 | Trial completion date: Apr 2029 --> Aug 2026 | Trial primary completion date: Sep 2027 --> Aug 2024

P1, N=40, Not yet recruiting, Guangdong Provincial People's Hospital

P3, N=147, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | N=220 --> 147

P2, N=35, Recruiting, Beijing Chest Hospital, Capital Medical University | Not yet recruiting --> Recruiting | Trial completion date: Dec 2026 --> Mar 2027 | Trial primary completion date: Dec 2025 --> Aug 2026

P2, N=25, Recruiting, Guangdong Provincial People's Hospital

P2, N=40, Recruiting, ImmunityBio, Inc. | Active, not recruiting --> Recruiting | N=147 --> 40

P3, N=100, Completed, Roche Farma S.A.

Baseline 68Ga-NOTA-WL12 PET/CT has a potential to predict the pathological response of neoadjuvant immunotherapy combined with chemotherapy in patients with resectable NSCLC, whose efficacy is comparable to that of therapy evaluations employing baseline and follow-up CT and 18F-FDG PET/CT examinations.

P1, N=100, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2027

P2, N=47, Not yet recruiting, Sun Yat-sen University

Oxymatrine reversed IFN-γ-induced upregulation of PD-L1 expression; moreover, it downregulated xCT and GPX4 protein levels in liver cancer cells and promoted intracellular Fe2+, ROS, and MDA levels. Oxymatrine promotes tumor immune response and ferroptosis in liver cancer by downregulating IFN-γ and synergistically enhances the inhibitory effect of anti-PD-L1 on liver cancer.

P3, N=238, Recruiting, Gruppo Oncologico del Nord-Ovest

P2, N=40, Recruiting, Anwaar Saeed | Not yet recruiting --> Recruiting

P3, N=49, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | N=100 --> 49

An immune/metabolism score integrating the features of six genes was developed as a predictive biomarker for immunotherapy response in multiple cohorts, allowing for the selection of patients most likely to experience positive outcomes from this therapy regimen. In conclusion, our study provides proof-of-concept data supporting the potential of SHR-1701 plus famitinib as an effective and safe subsequent-line therapy for refractory BTC and PDAC, highlighting the promise of targeting PD-L1, TGF-β, and angiogenesis pathways simultaneously.

P2, N=54, Recruiting, Abbisko Therapeutics Co, Ltd | Not yet recruiting --> Recruiting | Initiation date: Dec 2025 --> Nov 2024 | Trial primary completion date: Jun 2027 --> Dec 2027

P2, N=106, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed

In a first-in-human phase 1-2a study (GDFATHER-1/2a trial, NCT04725474 ), patients with advanced cancers refractory to anti-PD-1 or anti-PD-L1 therapy (termed generally as anti-PD-1/PD-L1 refractoriness) were treated with the neutralizing anti-GDF-15 antibody visugromab (CTL-002) in combination with the anti-PD-1 antibody nivolumab. Increased levels of tumour infiltration, proliferation, interferon-γ-related signalling and granzyme B expression by cytotoxic T cells were observed in response to treatment. Neutralizing GDF-15 holds promise in overcoming resistance to immune checkpoint inhibition in cancer.

These findings suggest that the mGPS measured at the time of radiologic PD can identify patients with a better prognosis who may benefit from continued atezolizumab therapy, aiding in the selection for TBP in clinical practice.

P2/3, N=542, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: May 2027 --> Dec 2025

P1, N=50, Not yet recruiting, FBD Biologics Limited | Initiation date: Sep 2024 --> Jan 2025

P2, N=26, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Oct 2025 --> Oct 2026

P2, N=401, Active, not recruiting, AstraZeneca | Trial completion date: Sep 2024 --> Sep 2025

P2, N=38, Not yet recruiting, Mehmet Akce

P1, N=72, Completed, Merus N.V. | Active, not recruiting --> Completed | N=238 --> 72 | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2024

P3, N=517, Active, not recruiting, UNICANCER | Trial primary completion date: Oct 2024 --> Jun 2025

P1/2, N=48, Not yet recruiting, University Health Network, Toronto

P3, N=110, Recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Jun 2025 --> Sep 2025

P2, N=20, Recruiting, University Medical Center Groningen | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: May 2024 --> Apr 2025

P1, N=42, Recruiting, Bio-Thera Solutions | Phase classification: P1a/1b --> P1 | Trial completion date: Jan 2024 --> Dec 2024 | Trial primary completion date: Jan 2024 --> Dec 2024

P2, N=30, Recruiting, Beijing 302 Hospital | Not yet recruiting --> Recruiting | Initiation date: May 2024 --> Oct 2024

Serum IL-6 levels are thought to be involved in the suppression of tumor immunity and are useful in predicting the therapeutic effect of Atezo+Bev treatment.

Clinical trials of ICI treatment including Nivolumab, Pembrolizumab, Avelumab have been conducted for metastatic GC (mGC). However, not all PD-L1 positive patients can benefit from it. It is urgent to find better biomarkers to predict the response of ICIs for more precise clinical treatment.