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Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
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Neuroendocrine tumours and their microenvironment.
Lotte D de Hosson1, Tim J Takkenkamp1, Gursah Kats-Ugurlu2
1Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, DA11, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
Cancer Immunology, Immunotherapy : CII
|April 10, 2020
Summary
Neuroendocrine tumors (NETs) show limited immune cell infiltration and lack key markers for immunotherapy response. Indoleamine 2,3-dioxygenase (IDO), tryptophan 2,3-dioxygenase (TDO), and cancer-associated fibroblasts contribute to a "cold" immune microenvironment in NETs.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Neuroendocrine tumors (NETs) can evade immune detection via programmed death-ligand-1 (PD-L1) and other immunosuppressive factors like regulatory T-cells (Tregs), indoleamine 2,3-dioxygenase (IDO), and tryptophan 2,3-dioxygenase (TDO).
- The interaction between NETs and their immune microenvironment, particularly in the context of immunotherapy, remains poorly understood.
Purpose of the Study:
- To investigate the immune microenvironment of serotonin-producing (SP-NET) and non-serotonin-producing NETs (NSP-NETs).
- To identify potential mechanisms contributing to immune suppression in NETs and explore factors relevant to immunotherapy response.
Main Methods:
- Immunohistochemical analysis of 33 SP-NET and 18 NSP-NET tumor samples.
- Assessment of programmed death-ligand-1 (PD-L1), T-cells, IDO, TDO, mismatch repair proteins (MMRp), and cancer-associated fibroblasts (CAFs).
Main Results:
- Programmed death-ligand-1 (PD-L1) expression was minimal (<1%) on tumor and T-cells. T-cells were present in only 33% of NETs.
- Indoleamine 2,3-dioxygenase (IDO) was expressed in 55% of SP-NETs and 22% of NSP-NETs (p=0.039). Tryptophan 2,3-dioxygenase (TDO) was expressed in 64% of SP-NETs and 13% of NSP-NETs (p=0.001).
- TDO-expressing stromal cells were identified as cancer-associated fibroblasts (CAFs). No loss of mismatch repair proteins (MMRp) was observed. Factors predicting immunotherapy response were limited.
Conclusions:
- Neuroendocrine tumors (NETs) exhibit a predominantly "cold" immune microenvironment, characterized by low T-cell infiltration and minimal PD-L1 expression.
- Indoleamine 2,3-dioxygenase (IDO), tryptophan 2,3-dioxygenase (TDO), and cancer-associated fibroblasts (CAFs) represent significant immunosuppressive mechanisms in NETs.
- Further research into these mechanisms is crucial for developing strategies to enhance anti-tumor immunity and improve clinical responses to immunotherapy in NET patients.
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