PDCD1 blocking peptide

Objectives The immune environment and the potential for neuroendocrine tumors (NETs) to respond to immune checkpoint inhibitors remain largely unexplored. We assessed immune checkpoint marker expression, lymphocytic infiltrate, and associated mutational profiles in a cohort of small intestine and pancreatic NETs. Methods We assessed expression of PDCD1 (PD-1), CD274 (PD-L1), and PDCD1LG2 (PD-L2) in archival tissue from 64 small intestine (SINETs) and 31 pancreatic NETs (pNET). We additionally assessed T-cell infiltrates, categorizing T-cell subsets based on expression of the T-cell markers CD3, CD8, CD45RO (PTPRC), or FOXP3. Finally, we explored associations between immune checkpoint marker expression, lymphocytic infiltrate, and tumor mutational profiles. Results Expression of PD-1 or PD-L1 in small intestine or pancreatic NET was rare, whereas expression of PD-L2 was common in both NET subtypes. T-cell infiltrates were more abundant in pNET than in SINET. We found no clear associations between immune checkpoint marker expression, immune infiltrates, and specific mutational profile within each tumor type. Conclusions Our findings provide an initial assessment of the immune environment of well-differentiated NETs. Further studies to define the immunologic differences between pNET and SINET, as well as the role of PD-L2 in these tumors, are warranted.

Objectives Tumor necrosis receptor super family (TNFRSF) plays an important role in regulating the function of CD8(+) T cells. In this study, we explored the clinical significance and immune profile of TNFRSF9(+) CD8(+) T cells in clear cell renal cell carcinoma (ccRCC) Methods The infiltration of immune cells was determined by immunohistochemistry in ZS cohort from our hospital and their prognostic value was further determined by Cox regression. Functional status of CD8(+) T cells in ccRCC was determined by flow cytometry in 29 fresh tumor samples. In silico analysis on a TCGA cohort and other datasets was performed to further demonstrate our findings. Results High TNFRSF9(+) CD8(+) T cells infiltration was associated with inferior overall survival in ZS cohort (p = .0016) and TCGA-KIRC cohort (p = .018). TNFRSF9(+) CD8(+) T cells expressed higher exhaustion markers (PD-1, TIM-3, CTLA-4, and TIGIT), and effector markers (IFN-gamma, GZMB, CD107a, and Ki-67), than their TNFRSF9 negative counterparts. In silico analysis indicated the expression of TNFRSF9 was significantly correlated with IFNG, GZMK, MKI-67, PDCD1, HAVCR2, TIGIT, and CTLA-4 in CD8(+) T cells. However, higher TNFRSF9 signature was correlated with larger tumor size shrinkage (p = .003) and better progression-free survival (p = .012) in patients treated with nivolumab but not everolimus. Conclusion TNFRSF9(+) CD8(+) T cells, which possessed both exhaustion and effector phenotype, were identified as an adverse prognosticator in ccRCC. These cells enrichment was associated with better immunotherapy response which indicated these cells potentially be crucial in immunotherapy.