Immune profiling of pituitary tumors reveals variations in immune infiltration and checkpoint molecule expression
- 25 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Pituitary
- Vol. 24 (3), 359-373
- https://doi.org/10.1007/s11102-020-01114-3
Abstract
Purpose Pituitary tumors are the second most common primary brain tumors. Functional tumors demonstrate increased PD-L1 expression, but expression of other checkpoint regulators has not been characterized. We sought to characterize the immune microenvironment of human pituitary tumors to identify new treatment opportunities. Methods 72 pituitary tumors were evaluated for expression of the immune regulatory markers programmed death ligand 1 (PD-L1), programmed death ligand 2 (PD-L2), V-domain Ig suppressor of T cell activation (VISTA), lymphocyte activation gene 3 (LAG3) and tumor necrosis factor receptor superfamily member 4 (OX40) by immunohistochemistry (IHC). Lymphocyte infiltration, macrophage infiltration, and angiogenesis were analyzed using IHC. Expression of pituitary tumor initiating cell marker CD15 and mismatch repair proteins MutS protein homolog 2 (MSH2) and MutS protein homolog 6 (MSH6) was also assessed. Results Pituitary tumors were infiltrated by macrophages and T cells, and they expressed varying levels of PD-L1, PD-L2, VISTA, LAG3, and OX40. Functional tumors and tumors with high expression of tumor stem cell markers had higher immune cell infiltration and greater expression of immunosuppressive checkpoint regulators. Increased PD-L1 and LAG3 and reduced VISTA were observed in primary tumors compared to recurrent tumors. Conclusion Immune cell infiltration and checkpoint regulator expression vary depending on functional status and presence of pituitary tumor initiating cells. Functional tumors may have a particularly immunosuppressive microenvironment. Further studies of immune checkpoint blockade of pituitary tumors, particularly functional tumors, are warranted, though combination therapy may be required.Keywords
Funding Information
- King Abdulaziz City for Science and Technology
This publication has 116 references indexed in Scilit:
- Loss of the signaling adaptor TRAF1 causes CD8+ T cell dysregulation during human and murine chronic infectionThe Journal of Experimental Medicine, 2011
- Microvesicles Released from Human Renal Cancer Stem Cells Stimulate Angiogenesis and Formation of Lung Premetastatic NicheCancer Research, 2011
- VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responsesThe Journal of Experimental Medicine, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Improved Survival with Ipilimumab in Patients with Metastatic MelanomaThe New England Journal of Medicine, 2010
- Tumor Infiltrating Lymphocytes But Not Serum Pituitary Antibodies Are Associated with Poor Clinical Outcome after Surgery in Patients with Pituitary AdenomaJournal of Clinical Endocrinology & Metabolism, 2010
- Glioma Tumor Stem-Like Cells Promote Tumor Angiogenesis and Vasculogenesis via Vascular Endothelial Growth Factor and Stromal-Derived Factor 1Cancer Research, 2009
- The significance of OX40 and OX40L to T‐cell biology and immune diseaseImmunological Reviews, 2009
- Role of Stat3 in suppressing anti-tumor immunityCurrent Opinion in Immunology, 2008
- OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejectionThe Journal of Experimental Medicine, 2008