Int J Clin Exp Pathol. 2021 Oct 15;14(10):1038-1047. eCollection 2021.
ABSTRACT
Immune checkpoint inhibitors have a significant role in oncology. One of these immune checkpoints is cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Inhibition of the CTLA-4 pathway has already led to the FDA approval of Ipilimumab (anti-CTLA-4), a targeted therapy for melanoma and other malignancies. CD137 is an inducible, costimulatory receptor of the tissue-necrosis-factor-receptor superfamily expressed on the activated immune cells. Clinical trials have also been set for anti-CD137 in several malignancies. We assessed CTLA-4 and CD137 expression on a tissue microarray (TMA) comprising of 99 core tissues which included normal, non-neoplastic, and neoplastic cervical lesions. When detected as strong granular cytoplasmic reaction in the epithelial cells, CTLA-4 expression was scored as positive. For CD137, the results were recorded based on the prese nce or absence of staining reaction on the cell membranes of the lymphoplasmacytic infiltrates. Overall, CTLA-4 was positive in 30% (30/100) of the cervical malignancies. Sub-categorically, 20% of invasive endocervical adenocarcinomas, 63% of adenosquamous carcinomas, and 31% of squamous cell carcinomas were positive for CTLA-4 with a tendency toward lower grade squamous cell carcinomas (SCCs). CD137 was positive in 100% lymphoplasmacytic infiltrates of endocervical adenocarcinomas, 90.5% of SCCs, and 87.5% of adenosquamous carcinomas. This study has found a significant expression of CTLA-4 in cervical cancer cells and CD137 positivity of lymphoplasmacytic infiltrates with potential for future targeted immunotherapy.
PMID:34760040 | PMC:PMC8569305
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