Background: In cancer, up-regulation of co-inhibitory B7 ligands is associated with immune evasion. So far, anti-PD-1 and anti-PD-L1 antibodies has been used in immune-oncology, with promising outcomes but only a small proportion of patients respond successfully. It is still needed identifying other markers, especially for endometrial cancer (EC). EC is a gynecological malignancy classified into two types, endometrioid type I and the most aggressive non-endometrioid type II. Up to now, very few information were provide about B7 members in EC. Furthermore, no molecular prognostic biomarkers are available for type II EC. Objective: Characterization of B7 members profile in EC and evaluation of PD-L2 prognostic impact in human type II EC biopsies. Methods: B7 members were evaluated in six human EC cell lines and one cancer-associated fibroblasts (CAFs), compared to normal endometrial samples. Additionally, using data from cBioportal, we performed a molecular profiling in a cohort of 506 patients. PD-L2 staining was evaluated in a cohort of 23 human type II EC samples, evaluating Overall Survival (OS) and Progression-Free Survival (PFS). Results: EC expresses several B7 members. PD-L2 was significantly over-expressed by one EC Type-I cell line and CAFs, ICOS-L and B7-H4 were expressed especially in mixed type I/II cell lines and type II patients. B7-H3 was expressed in EC cell lines and it was more expressed in type I patients. Additionally to these preliminary data, High PD-L2 expression correlated with shorter OS (p<0.033) but not with PFS (p>0.05). Conclusions: We firstly evidenced that some B7 members were expressed in EC with differences between Type I and Type II, compared with normal tissues. PD-L2 could be a potential predictive biomarker for Type II EC. These preliminary results suggest investigating better the B7 molecular role in EC.

Characterization of B7 members expression in endometrial cancer and clinical significance of PD-L2 in type II subtype

Oliviero Marinelli;Massimo Nabissi
2019-01-01

Abstract

Background: In cancer, up-regulation of co-inhibitory B7 ligands is associated with immune evasion. So far, anti-PD-1 and anti-PD-L1 antibodies has been used in immune-oncology, with promising outcomes but only a small proportion of patients respond successfully. It is still needed identifying other markers, especially for endometrial cancer (EC). EC is a gynecological malignancy classified into two types, endometrioid type I and the most aggressive non-endometrioid type II. Up to now, very few information were provide about B7 members in EC. Furthermore, no molecular prognostic biomarkers are available for type II EC. Objective: Characterization of B7 members profile in EC and evaluation of PD-L2 prognostic impact in human type II EC biopsies. Methods: B7 members were evaluated in six human EC cell lines and one cancer-associated fibroblasts (CAFs), compared to normal endometrial samples. Additionally, using data from cBioportal, we performed a molecular profiling in a cohort of 506 patients. PD-L2 staining was evaluated in a cohort of 23 human type II EC samples, evaluating Overall Survival (OS) and Progression-Free Survival (PFS). Results: EC expresses several B7 members. PD-L2 was significantly over-expressed by one EC Type-I cell line and CAFs, ICOS-L and B7-H4 were expressed especially in mixed type I/II cell lines and type II patients. B7-H3 was expressed in EC cell lines and it was more expressed in type I patients. Additionally to these preliminary data, High PD-L2 expression correlated with shorter OS (p<0.033) but not with PFS (p>0.05). Conclusions: We firstly evidenced that some B7 members were expressed in EC with differences between Type I and Type II, compared with normal tissues. PD-L2 could be a potential predictive biomarker for Type II EC. These preliminary results suggest investigating better the B7 molecular role in EC.
2019
The Immuno-Oncology 2019 World Congress (Immuno-Oncology2019)
274
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/427585
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