Here, we examined the anti-tumor efficacy and immunomodulatory effects of combining N-803 with an anti-PD-L1 antibody in preclinical models of solid carcinomas refractory to anti-PD-L1 or N-803.
Current molecular testing for selection of patients with gastrointestinal or pulmonary carcinomas relies on the prevalence of PD-L1 expression in tumor as well as immune cells by immunohistochemistry and/or on the evaluation of the microsatellite status.
The present work seeks to assess whether pancreatic carcinomas release exosomes which express c-Met (proto-oncogene mesenchymal-epithelial transition factor) and PD-L1 (programmed cell death 1 ligand 1), and whether the detection of such expression in serum has diagnostic or prognostic meaning for the affected patients.
Patients with salivary duct carcinomas and PD-L1 expressing TIICs showed a significantly worse DFS and OS (p = 0.022 and p = 0.003, respectively), those with both tumor cells and TIIC expressing PD-L1 a significantly worse DFS (p = 0.030).
Immune checkpoint inhibitors (ICIs), including inhibitors of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) have demonstrated prominent clinical benefits in a variety of cancers and have been rapidly applied to treat a variety of carcinomas such as melanoma, non-small-cell lung cancer, and head and neck cancer.
Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy.PD-L1 is also of prognostic impact.
Tumor cell PD-L1 expression was detected in 6 carcinomas, but not in any of the melanomas, whereas immune cells' expression of PD-L1 was seen in 17 carcinomas and 6 melanomas.
It was concluded that <sup>131</sup> I-PD-L1 mAb can be a potential theranostic candidate for visualizing of PD-L1 expression noninvasively and performing synergistic therapy in carcinomas.
CD274 (PDL1) and JAK2 (9p24.1) gene amplifications have been recently described in pulmonary carcinomas in association with programmed death-ligand 1 (PD-L1) expression.
There were 45 deficient MMR (dMMR) cases (8.2%), which showed higher rates of PD-L1 expression compared with MMR-proficient carcinomas (60.0% vs. 35.2%, P = 0.001).HER2 was positive in 66 (12.0%) cases.
High tumor mutation burden and strong PD-L1 staining may provide a rationale for the use of targeted immunotherapies in pulmonary sarcomatoid carcinomas.
We conclude that gastric carcinomas with lymphoid stroma show a spectrum of molecular changes and frequent PD-L1 expression, raising the possibility that this subgroup of tumors may be susceptible to checkpoint inhibitors and/or agents that target receptor tyrosine kinase-mediated signaling.
TC expression of PD-L1 was more common in NSCLC than in metastatic carcinomas (28% vs. 10%, p=0.009), while PD-L1-positive IC were present at relevant percentages (1-5%) exclusively in metastatic carcinomas (31% IC positive vs. 0%, p<0.001).
PD-L1 interpretation in genitourinary and head/neck carcinomas is reliable and reproducible among pathologists and across different tissue preparations.
Checkpoint inhibitors targeting the PD-1/PD-L1 axis are promising immunotherapies shown to elicit objective responses against multiple tumor types, yet these agents fail to benefit most patients with carcinomas.
In conclusion, PD-L1 overexpression is detectable in a substantial proportion of vulvar carcinomas in all stages independent of HPV and may be a suitable therapeutic target in these cancers.