PD-1-L

P2, N=24, Recruiting, Ever Supreme Bio Technology Co., Ltd. | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2022 --> Dec 2026

Cell counting kit-8 assay showed that PDP1 overexpression significantly raised MDA-MB-231 and MCF7 cell viability while STAT3 inhibitor S3I-201 recovered the cell growth to normal level. To summarize, PDP1 promotes the progression of BC through STAT3 pathway by regulating p-STAT3. The findings contribute to understanding the molecular mechanisms underlying BC progression, and opening avenues for targeted therapeutic approaches.

PD-1 expression on T-cells might serve as an adverse biomarker for lymphoma patients undergoing autologous stem cell transplantation, however further validation by larger prospective studies is required.

In vivo, the combination therapy induced more proliferative KLRG1-high PD1-low CD8+ T-cells and activated CD103+ DC in the tumor site and increased tumor-specific CD44+ CD8+ T-cells in the lymph node. Overall, the combination therapy of C-REV with 2'3'-cGAMP elicited antitumor immune memory responses and significantly enhanced systemic antitumor immunity in both treated and non-treated distal tumors.

Moreover, highly proliferative CD8 T cells in the B group had less PD-1 expression than those highly proliferative CD8 T cells in the DC group. The findings of this study suggest that B and DC could generate distinctive CD8 T cells, which potentially serve multiple purposes in cellular vaccine development.

Re-exposing the ex vivo-activated CD8+ T cells to tumor by adoptive transferring them to CT2A tumor-bearing mice revealed that BVax elicited immunological memory and potentiated GzmB+ production of CD8+ T cells. This study suggests that BVax and DC have distinctive interactions with CD8+ T cells, with the former poise CD8+ T cells at a more stem-like state, allowing them to differentiate upon tumor encounter.

To further demonstrate the role of PD-L1, we treated the PDL1-high expression cells MDA-MB-231, PD-L1 silenced MDA-MB-231 clones, and PD-L1 low expression cells MCF-7 with Durvalumab, an anti-PD-L1...Here, we further characterized the cellular autonomic role of PD-L1 in breast cancer and showed a differential role of basal PD-L1 expression in PD-L1 checkpoint inhibitors treatment efficacy. This suggests a potential role in monitoring PD-L1 expression indirect biomarkers (i.e. miR-320a, miR-145 and CD73) during ICIs treatment.

We present novel metrics of HER2 heterogeneity via HDmIF, which offer detailed characterization of the diversity of HER2 expression in a large, clinically-annotated cohort with long-term follow-up. Identification of a strong association between immunophenotype and RFS supports further investigation of the highly immune activated subsets of ER-/HER2+ breast cancer. Strong correspondence of HER2 IF and IHC and our HAIQu methodology offers a pathway to translation of HER2het metrics to clinical practice.

Immune-associated transcriptomic features, particularly CD8+ T cells were associated with pCR response to ICI in dMMR CRC. Heterogeneity of TME within dMMR CRC may help to discriminate patients with complete response to neoadjuvant ICI.

PDL1 is a latent prognostic factor in stage III BC and is closely related to some clinicopathological features. PDL1 expression in tumor tissues is significantly associated with better lifetime rate in stage III BC.

Results The multi-site blinded analysis across a cohort of 188 IO-treated patients (treated with nivolumab, pembrolizumab, atezolizumab or durvalumab) demonstrated the intra- and inter-tumoral heterogeneity of the PD-1/PD-L1 immune checkpoint engagement and notably showed no correlation between the extent of PD-1/PD-L1 interaction and PD-L1 expression (rs=0. This would both capture patients excluded from checkpoint immunotherapy (high PD-1/PD-L1 interaction but low PD-L1 expression, 24% of patients), and additionally avoid the treatment of patients resistant to this type of treatment (low PD-1/PDL1 interaction but high PD-L1 expression) who may benefit from alternative cancer therapeutics, such as other immunotherapies. Even at this early stage, QF-Pro® has set an unbiased quantitative cut-off to be considered for anti-PD-1/PD-L1 therapies which can be deployed directly into clinical practice.

In this study, we have demonstrated that the genes associated with immune checkpoint genes can be utilized as a prognostic biomarker for HCC. Notably, PD-1 gene expression in PBMCs has a great potential for estimating survival outcomes of patients with HCC.