PD-L1 expression

Mechanistically, Ubc13 deficiency leads to upregulation of Arg1 and PD-L1, the latter is modulated by reduced Ubc13-mediated K63-linked polyubiquitination and increasing activation of Akt, thereby inducing skewness to protumoral polarization and immunosuppressive manifestation. Taken together, we reveal that macrophage-intrinsic Ubc13 restrains lung tumor progression, indicating that activating Ubc13 in macrophages could be an effective immunotherapeutic regimen for lung cancer.

Neoadjuvant immunotherapy had a more significant therapeutic effect on stage IIIA-N2 NSCLC patients by reducing immunosuppressive and inflammatory factors, improving immune function, and reducing the occurrence of adverse reactions.

High PD-L1 protein expression was observed in ER-negative/HER2-negative BCBMs (48.3% vs 50.0% in local BCs, 21.4% in N-CNS). Our data highlights that a high proportion of BCBMs are potentially amenable to treatment with targeted therapeutic agents including PARP inhibitors and ICIs.

A 3-day-delay sequential combination might increase antitumor responses and clinical benefits compared with the simultaneous combination.

JAVELIN Renal 101 provides the longest follow-up to date for immune checkpoint inhibitor + tyrosine kinase inhibitor combination treatment from a phase 3 trial in aRCC. OS analyses favored avelumab + axitinib vs sunitinib but did not reach statistical significance; subsequent treatment may have impacted results. Avelumab + axitinib provided long-term efficacy benefits vs sunitinib, including prolonged PFS, a nearly doubled ORR, and more durable responses, with a manageable long-term safety profile.

Notably, ctDNA may offer valuable insights into the efficacy of T cell-engaging bispecific molecules, such as tebentafusp. The review provides a comprehensive overview of the evolving landscape of melanoma biomarkers, their role in personalizing treatment, and future research directions, including neoadjuvant immune checkpoint inhibition.

Blockade of the NLRP3 inflammasome led to reduced PD-L1 expression, fewer immunosuppressive cells, and suppressed tumor growth. These findings suggest that targeting the NLRP3 inflammasome-PD-L1 axis could be a novel treatment approach for ovarian cancer.

Furthermore, we find that HistoTME-predicted microenvironment signatures and their underlying interactions improve prognostication of lung cancer patients receiving immunotherapy, achieving an AUROC of 0.75 [95% CI: 0.61-0.88] for predicting treatment responses following first-line ICI treatment, utilizing an external clinical cohort of 652 patients. Collectively, HistoTME presents an effective approach for interrogating the TME and predicting ICI response, complementing PD-L1 expression, and bringing us closer to personalized immuno-oncology.

P3, N=700, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: May 2028 --> Jul 2025 | Trial primary completion date: Jan 2025 --> Jul 2025

P3, N=1080, Recruiting, Summit Therapeutics | N=400 --> 1080 | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Sep 2027 --> Dec 2027

P=N/A, N=38, Recruiting, Yunpeng Liu | Not yet recruiting --> Recruiting

P2, N=0, Withdrawn, University of Texas Southwestern Medical Center | N=46 --> 0 | Not yet recruiting --> Withdrawn

Additionally, it was observed that the expression of PD-L1 and CTLA-4 was interrelated (p < 0.001). This study demonstrated that MCT cells express both PD-L1 and CTLA-4 and that their expression was associated with MCT prognostic factors.

This study reveals that HIF-1α promotes FTO transcription under hypoxic conditions, thereby increasing PD-L1 expression through the PDK1/AKT/STAT3 axis. Inhibition of FTO and PDK1 under hypoxic conditions could serve as a promising immunotherapeutic strategy for breast cancer.

No abstract available

ORR and PFS were highly variable across sarcoma histologic subtype. In this large analysis, KS, ASPS, AS, MFS, and UPS demonstrated the highest ORR and longest PFS while osteosarcoma, SS, and LPS had the lowest ORR and shortest PFS. PD-L1 expression was also associated with increased ORR. Our findings provide further insight into understanding the sarcoma histologic and immunologic factors that correspond with response to ICIs.

Only myoCAFs were associated with higher rates of progression and recurrence in three independent cohorts (888 total patients), reaching prediction values comparable to transcriptomic classes, which we further validated using tissue micro-array. Our study provides a roadmap to establish the landscape of the NMIBC TME, highlighting myoCAFs as potential prognostic markers.

These patients with high FPG_Score were more likely to benefit from immunotherapy and had a more favorable prognosis. Our study innovatively provided a comprehensive analysis of FPGs in GC, and constructed the FPG_Score system for stratification of individual patients, so as to predict its benefit from immunotherapy and prognosis.

In this study, the biological attributes, expression patterns, and pathogenic mechanisms of Siglec-15 across various diseases were reviewed. The role of Siglec-15 in the pathogenesis and laboratory diagnosis of hematological disorders was also evaluated.

In conclusion, the therapeutic outcome supports the high-efficiency of radiotherapy based on BMS@Pt2Au4 NPs in hypoxic tumors expressing PD-L1.

P2, N=9, Active, not recruiting, National Cancer Institute (NCI) | N=27 --> 9 | Trial completion date: Oct 2024 --> Dec 2025

Furthermore, specific inhibitory ligand-receptor interactions, such as CLEC2D-KLRB1, CTLA4-CD86, and MIF-CD74, were exclusively identified in the RR-AITL TME. Our study provides a high-resolution characterization of the immunosuppression ecosystem and reveals the potential therapeutic targets for RR-AITL patients.

We detected 160 alterations with potential treatment implications, with 21.2% of samples showing alterations in the homologous recombination pathway. To the best of our knowledge, this study describes the largest cohort of pSCC with complex molecular-pathological, clinical, and prognostic analysis correlating with prognosis.

Due to the unique epitope, it demonstrates superior activation compared to APX005M (S267E)...Furthermore, in humanized transgenic mice challenged with huPD-L1-expressing tumor cells, BA4415 induced superior anti-tumor activity. This novel anti-PD-L1/CD40 bispecific antibody holds potential for strong anti-tumor therapeutic efficacy by selectively restricting CD40 stimulation in tumors.

Neither microsatellite instability nor mismatch-repair deficiency appear to play a role, but up to 62.2% of tumors express PD-L1. Currently, immune checkpoint inhibitors such as Avelumab and Ipilimumab, along with antibody-drug conjugates targeting TROP2 and Nectin‑4, are being tested in clinical trials, potentially leading to the approval of targeted therapies for metastatic penile carcinoma in the future.

PD-L1 expression in pre-treated EGFR T790 M + lung adenocarcinoma is not predictive of osimertinib efficacy, as demonstrated by in vitro, xenograft, and clinical case studies.

LKB1 and Skp2 are required for intact PD-L1 protein expression and TME remodeling in NSCLC. Inhibition of Skp2 resulted in a conversion from "hot" TME to "cold" TME and abrogated therapeutic outcomes of immunotherapy. Screening LKB1 and Skp2 status would be helpful to select recipients who may benefit from anti-PD-1/PD-L1 immunotherapy.

Inhibiting the expression of piRNA-137463 with AntagopiRNA-137463 suppressed tumor growth and metastasis via LOC100128494 in nude mice and enhanced the response of LUAD to anti-PD-1 therapy in immune-competent mice. In summary, this study elucidates the role of piRNA-137463 in the reprogramming of cholesterol metabolism, which drives the progression of LUAD, thereby identifying a new target for the comprehensive clinical management of LUAD.

P1, N=30, Recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Sep 2025 | Trial primary completion date: Oct 2024 --> Sep 2025

ΔT2 values increased over 4 weeks, correlating strongly with PD-L1 expression (P < 0.05). The PD-L1-targeted nanoprobe with MRI is a promising tool for noninvasive, real-time assessment of PD-L1 expression in MPM.

P2, N=70, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Nov 2025

This study elucidates the genomic characteristics of PD-L1-induced resistance to EGFR-TKIs. For patients with concurrent mutations in EGFR and PD-L1 expression, a first-line treatment strategy combining EGFR-TKIs with chemotherapy may offer a more effective alternative.

P1/2, N=136, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | N=232 --> 136 | Trial primary completion date: Aug 2026 --> Dec 2024

After undergoing concurrent chemoradiotherapy, the patient received six cycles of treatment with toripalimab in combination with paclitaxel and platinum-based agents. The 2-year PFS rate was higher in patients with PD-L1 combined positive score (CPS)≥10 compared to those with CPS<10 (92.4% vs 81.2%, χ²=0.68, P=0.409), and higher in patients with low tumor mutation burden (TMB-L) compared to those with high tumor mutation burden (TMB-H) (95.2% vs 83.3%, χ²=1.91, P=0.167). Patients with locally advanced cervical cancer can achieve favorable objective response rates when treated with toripalimab in combination with platinum-based concurrent chemoradiotherapy and consolidative chemotherapy.

A range of monoclonal antibodies, including avelumab, atezolizumab, camrelizumab, dostarlimab, durvalumab, sinitilimab, toripalimab, and zimberelimab, have been developed for targeting the interaction between PD-1 and PD-L1. Moreover, the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules. Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.

Importantly, targeting GMPS with angustmycin A, an inhibitor of GMPS activity, significantly suppressed PD-L1 expression and tumor growth in HCC, which also increased the sensitivity to anti-CTLA-4 immunotherapy. These findings suggested the potential of targeting GMPS as a promising therapeutic approach for HCC.

Mechanistically, SNHG16 acted as a competitive endogenous RNA to enhance ELK4 expression by sponging miR-324-3p, thereby provoking the transcription of PD-L1. Our results demonstrated that SNHG16 silencing led to the suppression of cell growth, metastasis, and immune escape of CRC cells through mediating miR-324-3p/ELK4/PD-L1 axis, offering promising targets for CRC treatment.

While NSCLC survival in Greenland has improved over the past decade, significant challenges remain. The trend towards diagnosing more stage IA-IIIA patients and the recent improvements in diagnostic and therapeutic options in Greenland are expected to translate into a better prognosis in the coming years. Addressing diagnostic delays and enhancing treatment options are crucial steps toward improving outcomes for NSCLC patients in Greenland.

The combination of Tislelizumab and Sorafenib demonstrates promising antitumor activity in the first-line treatment of hepatocellular carcinoma, with a relatively high objective response rate (ORR) and acceptable safety profile. Baseline CTC PD-L1 positivity can serve as a predictive marker for selecting hepatocellular carcinoma patients for PD-1/PD-L1 blockade therapy, and dynamic measurement of CTC changes can be used to monitor treatment efficacy.

In each case, checkpoint blockade led to durable radiographic responses. We therefore propose that it is reasonable to assess combined positive score and tumor mutational burden in refractory or recurrent pancreatic cancers when initiation of ICB is being considered.

This correlation implies an enhanced antigen presentation process that may be unleashed by blocking these two immune checkpoints. Our results highlight the significance of PD-L2 as an essential immune checkpoint alongside PD-L1 and emphasize its potential as a target for bolstering antitumor immunity in colorectal cancer.

ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer.