Herein, we set up a novel and robust screening system to identify small molecular compounds which downregulate the PD-L1 level of tumor cell based on Odyssey on/in cell quantitative immunoblots technology.
We, for the first time, showed that AF increased CD8<sup>+Ve</sup> T-cell tumor infiltration in vivo and upregulated immune checkpoint PD-L1 expression in an ERK1/2-MYC-dependent manner.
Melanoma is a deadly tumor which in recent years has been successfully treated with immune checkpoint inhibitors as PD-1/PD-L1 and CTLA-4 inhibitors and targeted therapy as BRAF and MEK inhibitors.
These spatial light-patterns can be automatically configured to profile (1) "tumor-only" cells plus "tumor-microenvironment-only" cells; (2) unique cell types and rare cell features (e.g., macrophages, CD8, CD3, CD45, PD-L1 on macrophages, PD-L1 on tumors, etc.); (3) spatial gradients around cell-features or tumor features (e.g., excluded boundaries); (4) hypothesis-free spatial grids; (5) simple hand-selected geometric areas (e.g., free-hand software-based "drawing" on tissue regions); and (6) or any combination of the above modalities.
Allele frequency-adjusted blood-based tumor mutational burden as a predictor of overall survival for non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitors.
We found that Lmdd-MPFG promoted the expression of PD-L1 in HCC cells but resensitized the tumor local T cell to respond to the anti-PD-1 immunotherapy.
All the biodistribution, PET imaging, autoradiography and immunohistochemical staining studies revealed that the tracer <sup>68</sup>Ga-NOTA-Nb109 specifically accumulated in A375-hPD-L1 tumor with a maximum uptake of 5.0 ± 0.35 %ID/g at 1 h. <b>Conclusion:</b> The tracer <sup>68</sup>Ga-NOTA-Nb109 holds great potential for noninvasive PET imaging of the PD-L1 status in tumors and timely evaluating the therapeutic effect of immune checkpoint targeting treatment.
In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of PD-L1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion.
In addition, the high levels of PD-L1 were significantly associated with increased tumor lymphatic metastasis (P ≤ .05), tumor staging (P ≤ .01), as well as BRD4 expression (P ≤ .05).
Evaluation of PD-L1 expression in paired histologic and cytologic tumor specimens shows comparable results if a deviation of 10% between the values is tolerated.
Regardless of the remarkable clinical success of immune checkpoint blockade (ICB) against PD-1/PD-L1 pathway, this approach has encountered drawbacks in most patients due to the activation of tumor immunosuppressive factors such as myeloid-derived suppressor cells (MDSCs).
Recently, tumor mutational burden has emerged as an alternative biomarker, and studies have demonstrated its utility, irrespective of the PD-L1 level of a tumor.
One hundred twenty-two tumor specimens were analyzed by immunohistochemistry (IHC) to intra-tumor immune cells and programmed death protein ligand 1(PD-L1) expression on tumor cells.
This suggests that the total number of PD-L1-expressing cells, including tumor and immune cells, is a more sensitive prognostic biomarker than the number of PD-L1-expressing tumor cells in GC.