PD-L1 (Programmed death ligand 1)

P1, N=160, Recruiting, SystImmune Inc. | N=120 --> 160

P=N/A, N=58, Active, not recruiting, Wake Forest University Health Sciences | Recruiting --> Active, not recruiting | N=244 --> 58

P2, N=15, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Jul 2026 --> Jul 2027

P1/2, N=15, Suspended, Cancer Research UK | Trial completion date: Mar 2029 --> Oct 2026

P1/2, N=117, Active, not recruiting, Cantargia AB | Trial primary completion date: Jun 2025 --> Apr 2026

P1/2, N=29, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting

This study suggests that administering chemotherapy prior to immunotherapy appears to improve OS in patients with advanced EC and GC, particularly when initiated as first-line treatment. These findings highlight the need for further research into biomarkers and personalized treatment strategies to enhance patient outcomes.

Future directions include multicenter prospective trials to validate multimodal models, standardize detection methods, and increase interdisciplinary collaboration. By integrating genomic, epigenetic, metabolic, and microbiome data, these models can better capture the complexity of PDAC, thereby improving patient outcomes through precision immunotherapy.

Moreover, the synergistic mechanisms with immunotherapy remain largely hypothetical, supported by limited in vivo studies. By addressing these barriers through interdisciplinary collaboration, FLASH-RT may eventually advance precision radio-immunotherapy, but substantial translational research is still required before it can supplant conventional paradigms.

A prospective, non-randomized, two-cohort study was designed to evaluate the efficacy of sintilimab combined with chemotherapy in this setting...This preliminary analysis demonstrates that ICI combined with chemotherapy provides durable antitumor activity and a manageable safety profile as neoadjuvant and/or adjuvant therapy for locally advanced PSCC. These results warrant further validation in larger cohorts.

Finally, radiation-induced metabolic stress may shift nucleotide-sugar availability (including HBP-derived UDP-GlcNAc), linking metabolic state to glycosylation programs and radiosensitivity. We conclude by outlining therapeutic opportunities as well as practical hurdles-such as specificity, toxicity, and delivery-that must be addressed before glycosylation-targeted radiosensitization can be translated to the clinic.

Beyond intracellular signaling, S-palmitoylation reshapes the tumor microenvironment (TME) by regulating the transport and degradation of immunomodulatory factors, notably promoting immune evasion by inhibiting the lysosomal degradation of programmed death-ligand 1 (PD-L1). This review synthesizes recent advances through three unique organizing pillars: (i) the bidirectional metabolic-palmitoylation feedback loops, (ii) palmitoylation-driven epigenetic plasticity, and (iii) the paradigm shift toward substrate-centric therapeutic designs, aiming to overcome current clinical challenges and enhance the efficacy of immunotherapy.