Expression of PD-L1 in digestive neuroendocrine neoplasms and its correlation with clinicopathologic features. Exploring its potential role as prognostic marker and possible target for anti-PD-1/PD-L1 therapy.
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UNIL restricted access
State: Public
Version: author
License: Not specified
Serval ID
serval:BIB_277C8AA3EC92
Type
A Master's thesis.
Publication sub-type
Master (thesis) (master)
Collection
Publications
Institution
Title
Expression of PD-L1 in digestive neuroendocrine neoplasms and its correlation with clinicopathologic features. Exploring its potential role as prognostic marker and possible target for anti-PD-1/PD-L1 therapy.
Director(s)
LA ROSA S.
Codirector(s)
SEMPOUX C.
Institution details
Université de Lausanne, Faculté de biologie et médecine
Publication state
Accepted
Issued date
2021
Language
english
Number of pages
27
Abstract
Background
Digestive neuroendocrine neoplasms (NENs) are heterogeneous, encompassing a broad spectrum of neoplasms ranging from indolent well-differentiated neuroendocrine tumors (NETs) to highly aggressive neuroendocrine carcinomas (NECs). The PD-1/PD-L1 pathway plays a pivotal role in T cells activation and host immune response to cancer. PD-L1 expression in tumor and/or immune cells has been suggested as a prognostic biomarker in different type of cancers, allowing the identification of patients who can be treated with targeted checkpoint inhibitors. However, the prognostic role of PD-L1 expression in digestive NENs is still unclear.
Methods
We investigated PD-L1 expression using the SP263 antibody (Ventana Medical System) in 68 well- characterized digestive NENs: 32 NETs and 36 NECs. TPS and CPS PD-L1 scores, tumor infiltrating lymphocytes (detected using the anti-CD3, CD4, and CD8 antibodies), and mismatch repair (MMR) protein expression (detected using the anti-hMLH1, hMSH6, and hPMS2 antibodies) were evaluated. Immunohistochemical findings were correlated with clinicopathological features.
Results
PD-L1 scores TPS >1% and/or CPS >1 were observed in 5/32 NETs and 23/36 NECs (p: 0.05). The mean TPS score in positive cases was 6.3% and 14% in NETs and NECs, respectively. The CPS score was 4.8 and 7.91 in NETs and NECs, respectively. MMR-deficient neoplasms were more frequently observed in NECs than in NETs (2 NETs and 5 NECs, p: <0.05). No correlation between PD-L1 expression and survival or other clinicopathological parameters was found, including Ki67-proliferative index and MMR-deficiency. Intra- tumor immune infiltration was statistically more abundant in NECs than in NETs.
Conclusion
The heterogeneous expression of PD-L1 in NENs, with only a few positive cases among NETs, suggests that targeted checkpoint inhibitors therapy might have a potential role only in selected cases, mainly in NECs. T-cell infiltrate is more abundant in NECs than in NETs, supporting the possible application of immunological therapy in NECs.
Digestive neuroendocrine neoplasms (NENs) are heterogeneous, encompassing a broad spectrum of neoplasms ranging from indolent well-differentiated neuroendocrine tumors (NETs) to highly aggressive neuroendocrine carcinomas (NECs). The PD-1/PD-L1 pathway plays a pivotal role in T cells activation and host immune response to cancer. PD-L1 expression in tumor and/or immune cells has been suggested as a prognostic biomarker in different type of cancers, allowing the identification of patients who can be treated with targeted checkpoint inhibitors. However, the prognostic role of PD-L1 expression in digestive NENs is still unclear.
Methods
We investigated PD-L1 expression using the SP263 antibody (Ventana Medical System) in 68 well- characterized digestive NENs: 32 NETs and 36 NECs. TPS and CPS PD-L1 scores, tumor infiltrating lymphocytes (detected using the anti-CD3, CD4, and CD8 antibodies), and mismatch repair (MMR) protein expression (detected using the anti-hMLH1, hMSH6, and hPMS2 antibodies) were evaluated. Immunohistochemical findings were correlated with clinicopathological features.
Results
PD-L1 scores TPS >1% and/or CPS >1 were observed in 5/32 NETs and 23/36 NECs (p: 0.05). The mean TPS score in positive cases was 6.3% and 14% in NETs and NECs, respectively. The CPS score was 4.8 and 7.91 in NETs and NECs, respectively. MMR-deficient neoplasms were more frequently observed in NECs than in NETs (2 NETs and 5 NECs, p: <0.05). No correlation between PD-L1 expression and survival or other clinicopathological parameters was found, including Ki67-proliferative index and MMR-deficiency. Intra- tumor immune infiltration was statistically more abundant in NECs than in NETs.
Conclusion
The heterogeneous expression of PD-L1 in NENs, with only a few positive cases among NETs, suggests that targeted checkpoint inhibitors therapy might have a potential role only in selected cases, mainly in NECs. T-cell infiltrate is more abundant in NECs than in NETs, supporting the possible application of immunological therapy in NECs.
Keywords
PD-L1, neuroendocrine neoplasm, prognosis, digestive system, neuroendocrine tumors, neuroendocrine carcinomas
Create date
12/09/2022 11:15
Last modification date
27/09/2023 6:59
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