PD-L1-H

This AMC-based nomogram could provide better recurrence stratification. Immunosuppression in tumors with high AMC infiltration might contribute to promoting tumor progression.

In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.

Furthermore, we explored the genomic features in determining the benefits of ICIs treatment and found that patients with pDCB were associated with higher tumor immunogenicity. The DCB model constructed in this study can effectively predict the efficacy of ICIs treatment in patients with melanoma, which will be helpful for clinical decision-making.

Conclusions. Coexpression of PD-L1/PD-1 with CXCR3/CD36 in circulating lymphocytes and serum IL-19 levels contributes to poor prognosis and might be potential markers for extranodal involvement in lymphoma.

In para-cancerous tissues, biological processes of immune response and cell chemotaxis were downregulated, and the proportion of tumor-killing immune cells was decreased. Worse inflammation and fibrosis in non-cirrhotic HBV-associated HCC is associated with worse prognosis, which may reflect more aggressive tumor behavior and an immunosuppressed, pro-metastatic tumor microenvironment.

sPD-L1 mainly consisted of secPD-L1, and its level was higher in patients with distant metastasis, especially distant lymph node metastasis and positive CPS. sPD-L1 is a potential dynamic marker to identify rapid progression on combination immunotherapy and avoid ineffective treatment for pMMR CRC.

In human translational studies, TIGIT signaling blockade in vitro enhances neoantigen-specific T cell function following vaccination. Taken together, preclinical and human translational studies support testing neoantigen vaccines in combination with therapies targeting the PD-1 and TIGIT signaling pathways in patients with PDAC.

PDL1-harboring gastric cancer had increased susceptibility to αPDL1. The value of this drug-controlled release system targeting the tumor microenvironment in immune checkpoint therapy of gastric cancer would provide a scientific basis for clinically applying nucleic acid drugs.

A PFS-optimized regimen may improve disease control rates ≥15%. Pembrolizumab beyond progression may benefit a subset of patients with PD-L1-high, driver alteration-free NSCLC, but prospective studies are warranted.

Our data demonstrate that circ_0000052 is oncogenic, and the circ_0000052/miR-382-3p/PD-L1 axis is critical in HNSCC progression. The manipulation of circRNAs/miRNAs in combination with anti-PD-L1 therapy may improve personalized disease management.

NCT04262856

TMB-H and PD-L1-H were common in dMMR solid tumors (164/209 [78.5%] and 108/209 [51.7%], respectively); PD-L1-H was observed in 39.4% (56/142) of MMRp EC tumors. Objective response rate (ORR) (95% CI), per RECIST v1.1 assessed by blinded independent central review, was higher in pts with TMB-H/PD-L1-H tumors (n=99; 55.6% [45.2–65.5]) than pts with TMB-low (L)/PD-L1-L tumors (n=51; 7.8% [2.2–18.9], respectively), or pts with TMB-L/PD-L1-H (n=57; 17.5% [8.7–29.9]) or TMB-H/PD-L1-L tumors (n=32; 25% [11.5–43.4]). ORR (95% CI) was 44.7% (34.9–54.8), 38.7% (29.4–48.6), and 13.4% (8.3–20.1) for Cohorts A1, F and A2, respectively.

PD-L1-H and TMB-H were frequently observed in dMMR cohorts, regardless of tumor type. PD-L1-H was also prevalent in MMRp EC tumors. Although not powered to assess antitumor activity, ORR was higher in pts with TMB-H and PD-L1-H solid tumors.

sPD-L1 could represent a non-invasive biomarker that is easily dosable in the blood of patients. The pooled data from the selected studies showed that a high circulating concentration of sPD-L1 in cancer patients correlates with worse survival, suggesting that it may be a helpful prognostic biomarker for the selection of cancer patients before immunotherapy, thus improving the efficacy of ICIs and avoiding unnecessary treatment.

The CAR pNK cells and nivolumab resulted in a synergistic anti-solid tumor response. Together, our study highlights a robust platform to develop and evaluate the antitumor efficacy and safety of previously unexplored therapeutic regimens.

P2, N=300, Recruiting, GlaxoSmithKline | Not yet recruiting --> Recruiting

In conclusion, sPD-L1 was a negative independent prognostic factor for MDS patients at the time of diagnosis. High levels of sPD-L1 were presented in patients with lower hemoglobin and higher risk group, associating with disease progressing.

Our results suggest that elevated preoperative sPD-L1 level is a predictor of higher pathological tumor stage and worse survival in UTUC, which therefore may help to optimize therapeutic decision-making. The observed characteristic sPD-L1 flare during immune checkpoint inhibitor therapy may have clinical significance.

The status of lymph node metastasis, SUVmax, and SUVmean of the primary lesion correlated with PD-L1 levels in CCRCC. A combination of lymph node metastasis status and SUVmean could be utilized to predict PD-L1 levels, thus allowing monitoring of a tumor's immunotherapy response.

Our data revealed a subset of patients with ESCC harbored DDR gene mutations. Patients with these DDR gene mutations are significantly associated with immune biomarkers, implying the potential feasibility of combining DDR agents with immunotherapy in patients with DDR deficiency.

Collectively, we identified the prognostic value of EPM2A in PCa via a bioinformatics method. Patients with higher EPM2A may be more sensitive to immunotherapy, and patients with lower EPM2A were more suitable for bicalutamide, cisplatin and paclitaxel therapy.

Conclusions High CTLA4 or GITR in the context of low PDL1 may represent an intermediate-T cell-inflamed TME and/or tumor cell-intrinsic expression. Stratification of tumors by T cell-inflamed gene signature, or PDL1 status, as well as expression of a specific therapeutic target may identify patient populations who could benefit from CTLA4 or GITR depletion strategies in IO combination therapies.

P2, N=300, Not yet recruiting, GlaxoSmithKline

P2, N=300, Ongoing, GlaxoSmithKline Research & Development Limited

PDL1-H and TMB-H were frequently observed in the dMMR EC and non-EC cohorts, regardless of tumour type; PDL1-H was also prevalent in MMRp EC tumours. Although not a powered analysis, ORR by BICR per RECIST v1.1 was higher in patients with TMB-H and PDL1-H solid tumours. Across cohorts, dMMR status was predictive of response.

Adjuvant ATZ following chemotherapy results in population-level reduction of PDL1 high eNSCLC locoregional recurrence or distant metastasis. Further research will assess the impact of this clinical improvement on economic and societal burden associated with the recurrent NSCLC.

Abnormal levels of laboratory parameters and intensified tumor burden can be expected if elevated baseline plasma PD-1/PD-L1 levels are found.

We found a significant correlation between the levels of sTGF-beta and sPD-L1 before first-line chemotherapy. These findings support the possible interaction of TGF-beta and PD-L1 pathways and suggest that sTGF-beta and sPD-L1 might synergize and be new potential blood-based biomarkers.

Crizotinib use was limited across all subgroups...Table: 1112P a 87 pts had real-world progression assessment; b Real-world progression assessed as part of routine clinical care (physician's interpretation of radiology reports abstracted from clinic visit notes; decision based on radiology and/or clinical assessment) NR=Not reached; SOC=standard of care Conclusions This study provides insights into tx and outcomes of pts with METex14 in view of observed PD-L1 status. Due to sample size limitation, clinical outcomes observed in this study should be further validated in larger cohorts and in pts receiving newer generation MET inhibitors.

Conclusion These findings agree with in vivo & clinical data showing an association between Gal-3 expression & lack of efficacy of PD1/PDL1 targeted checkpoint inhibitors. 1 Li et al Biomedicines 2021 2 Capalbo et al Int J Mol Sci 2019 3 Vuong et al Cancer Res 2019 4 Zhang et al FEBS Open Bio 2020

The results indicated that lung cancer patients with higher ADAMTS8 levels among wild-type EGFR or low PD-L1 groups survive longer than those with lower levels do. This study indicates that ADAMTS8 might be a treatment option for patients with lung adenocarcinoma who lack efficient targeted or immunotherapies.

Together, we provide evidence that IL6 induced mtDNA leakage to regulate the immune escape of EC cells. Our findings may provide a novel clue for the development of therapeutic targets for EC.

They also had a high level of PD-L1 protein expression (p < 0.01), number of neoantigens (p < 0.001), and TMB (p < 0.001), implying the possible prediction of IRBPS in the immunotherapy of LUAD. The currently established IRBPS encompassing immune-related RBPs might serve as a promising tool to predict survival, reflect the immune microenvironment, and predict the efficacy of immunotherapy among LUAD patients.

Our results suggest that AML genotype is related to blast immunophenotype, and that high TIM-3 transcript levels in AML blasts could be a marker of immune escape. Cellular pathways regulating resistance to the immune system might contribute to the predicted response to standard therapy of patients in specific AML subgroups and should be targeted to improve AML treatment.

Treg PD-1 engages LEC PD-L1 to regulate lymphatic TEM. Treg PD-1 signals through LEC PD-L1 to induce the PI3K/Akt pathway to modulate cell junctions, and through classical NFκB-p65 to regulate VCAM-1 expression. The modulated LEC structures uniquely affect only Treg but not Teff TEM.

Interestingly, stroma-associated PD-L1 cells frequently have intracellular hyaluronan. Collectively, data presented in this study suggest that the interplay between tumor-recruited myeloid cells and stromal HA may contribute to the inflammation and immune tolerance in kidney cancer.

In patients with NSCLC and PD-L1 ≥50%, the ORR and mPFS to first-line pembrolizumab were similar between patients < vs ≥80 years old. OS was shorter among patients ≥80y, potentially reflecting lower use of second-line therapy in elderly patients after progression on pembrolizumab. The immunophenotypic correlates of NSCLC in older patients need further investigation.

Many clinical trials of LAG3 inhibitors have had modest effects, but recent data suggests that the LAG3 antibody relatlimab together with nivolumab (anti-PD1) provided greater benefit than nivolumab alone in patients with melanoma. High LAG3 was found in almost a quarter of tumor samples and significantly associated with other immune checkpoints with FDA-approved drugs. Ongoing studies combining LAG3 inhibitors and specific immune checkpoint inhibitors may yield more clinical benefit if individualized immunomic transcript interrogation is undertaken, rather than population-based approaches without employment of rationally combined agents matched to each patient’s cancer.

In this real-world database, SWI/SNF alterations were associated with a significantly worse prognosis. There was no association with increased genomic instability of PDAC tumors, and in the cases with linked treatment data, there was no association with response to PARPi’s or ICI’s.

Except in the subgroup of never-smoker patients, sparing the chemotherapy in first-line CIT treatment does not appear to impact survival outcomes in Nsq-NSCLC patients with high PD-L1 expression.

Secretory DCs are linked to good prognosis in head and neck squamous cell carcinoma, and to response to checkpoint blockade in Melanoma. Hence, the functional dichotomy of DCs we describe has both fundamental and translational implications in inflammation and immunotherapy.

Conclusions These studies reveal potent anti-tumor activity, both in vitro and in vivo, of BAY1688/ATA3271 allogeneic CAR-T cells generated using an original and an optimized manufacturing process. Overall, BAY1688/ATA3271 may be a promising approach for the treatment of MSLN-positive malignancies, and this data warrants further development of this program towards clinical trials.