Monoclonal antibodies directed against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting

The gap

Consensus across the literature

Supporting evidence — 3 representative gaps

• Emerging Therapeutic Strategies in Metastatic Hormone-Sensitive Prostate Cancer (2026) · doi

  Advancements in immunology and the mechanisms of tumor immune evasion have positioned immuno- therapy as a revolutionary treatment approach across oncology, as seen in melanoma, renal cell carcinoma, breast cancer, and lung cancer.[54] These outcomes sparked interest in immunotherapy for metastatic prostate cancer. In this review, we will focus on immune checkpoint inhibitors (ICIs). Programmed death (PD) inhibitors, such as nivolumab and pembro- lizumab, enable immune targeting of tumor cells. Following an immune response, the immune system downregulates itself via cytotoxic T-lymphocyte–asso- ciated protein 4 (CTLA-4). CTLA4 inhibitors like ipili- mumab perpetuate the immune response to target tumor cells.[55] In 2011, the FDA first approved ipili- mumab for advanced melanoma, as it demonstrated improved OS.[56] Immunotherapy in metastatic castration- resistant prostate cancer (mCRPC) Despite the success in other tumor types, trials assess- ing the efficacy of immunotherapy in prostate cancer have not been compelling. In 2014, Kwon et al[57] found no difference in OS in patients with mCRPC who pro- gressed after chemotherapy and received ipilimumab, although they noted a slight benefit in PFS. These results were largely replicated in 2016 in chemotherapy-naive mCRPC, although with slightly improved PFS and PSA response rates.[58] For pembrolizumab, the phase 1b KEYNOTE-028 trial showed initial promise against mCRPC.[59] Of the 23 patients who received pembrolizumab, 4 had partial responses (objective response rate [ORR] 17.4%, 95% CI, 5.0%–38.8%). Pembrolizumab resulted in a mean duration of response of 13.5 months and increased median PFS and OS in heavily pretreated programmed death ligand 1 (PD-L1)-positive mCRPC. The subse- quent phase II KEYNOTE-199 trial evaluated pembroli- zumab in mCRPC with prior docetaxel and one or h t t p : / / c r e a t i v e c o m m o n s . o r g / l i c e n s e s / b y - n c - n d / 4 . 0 / l D o w n o a d e d f r o m h t t p s : / / i n n o v a t i o n s o u r n a s - j i l j l p o . k g m e r i d a n . c o m a t i 2 0 2 6 - 0 7 - 0 6 i v a O p e n A c c e s s . i T h s w o r k i s p u b l i s h e d u n d e r - - a C C B Y N C N D 4 - . 0 I n t e r n a t i o n a l i L c e n s e .

  Keywords: immune mcrpc cancer response tumor immunotherapy prostate inhibitors pembrolizumab melanoma metastatic programmed death cells ctla
• Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks (2024) · doi

  Over the past decade, ICIs have been developed and approved for clinical use in multiple cancer types at an unprecedented rate. Despite tremendous progress, ICIs have not completely solved the problem of cancer treatment. Besides discovering biomarkers to predict the efficacy and safety of ICIs, more immune checkpoint molecules may need to be identified in the next decade to provide more options for immunotherapy and bring treatment opportunities to more patients, which depends on our insights into the mechanisms of immune checkpoint regulation. This review sum- marizes the status quo of frequent immune checkpoints and ICIs commonly applied in cancer, such as anti-PD-1/PD-L1, anti-CTLA-4, anti-LAG-3, anti-TIM-3, and other immune checkpoints targeted mAbs. The regulatory mechanisms of immune checkpoints are complex and unclear, which stem from its complicated and diverse influencing factors, involving ncRNAs, proteins, and other elements. As a class of abundant component of the human transcriptome involved in cancer hallmarks, ncRNAs are closely associated with the expression regulation of the structure’s stability, circRNAs present significantly greater advantages and potential as diagnostic and prognostic biomarkers for cancer management than other types of ncRNAs. Also, circRNAs have been confirmed to involve in various cancer hallmarks including prolifera- tion, cell death, inflammation, angiogenesis, invasion and metastasis interacting with proteins, through functioning as miRNA sponge, encoding proteins, or other unclarified mechanisms. immune checkpoints.

  Keywords: cancer immune icis checkpoints anti mechanisms ncrnas proteins decade types treatment biomarkers checkpoint regulation hallmarks
• Genomic correlates of response to CTLA-4 blockade in metastatic melanoma (2015) · doi

  Monoclonal antibodies directed against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting immune checkpoint activity, but clinical predictors of response to these therapies remain incompletely characterized.

  Keywords: clinical monoclonal antibodies directed against cytotoxic lymphocyte associated antigen ctla ipilimumab yield considerable benefit patients