Research Article: Dominant T cell receptor clonotypes in adrenocorticotropic hormone-secreting pituitary carcinoma are the highest-frequency clones among CD4 + and CD8 + cells in peripheral blood during effective anti-PD-1 therapy
Abstract:
Pituitary carcinoma is a rare and highly aggressive tumor. While anti-programmed cell death-1 (PD-1) therapy has shown efficacy in some cases, the factors that predict a favorable response remain largely unclear.
To evaluate tumor-infiltrating lymphocytes (TILs) in pituitary carcinoma and to compare T?cell receptor (TCR) clonotypes between the pituitary and peripheral blood.
A 34-year-old woman with Lynch syndrome and adrenocorticotropic hormone-secreting pituitary carcinoma with hepatic metastasis received anti-PD-1 therapy, achieving durable disease control exceeding 1 year. Immunohistochemistry was performed on treatment-naïve surgical tumor samples, and TCR repertoire analyses were conducted on both the tumor sample and peripheral blood mononuclear cells collected during effective anti-PD?1 therapy.
Treatment-naïve pituitary carcinoma tissues exhibited infiltration of CD4 + and CD8 + T cells. Analysis of the TCR repertoire identified 15 clonotypes with a high frequency (> 1% of sequencing reads) in the tumor; among these, four of the five most prevalent clonotypes were co-detected as dominant clones in peripheral blood after treatment, including the most abundant clones found within the CD4 + and CD8 + T cell populations. Despite control of the primary and hepatic lesions, ovarian metastasis developed, which was associated with reduced CD4 + TILs.
The presence of CD4 + and CD8 + TILs may underlie the immunological foundation for PD-1 blockade efficacy in pituitary carcinoma, supported by the detection of tumor-resident TCR clonotypes in peripheral blood during a positive therapeutic response.
Introduction:
Pituitary carcinoma is a rare (accounting for only 0.1–0.5% of all pituitary tumors) and highly aggressive malignancy defined by the presence of distant metastases ( 1 ). It has also been reported in patients with Lynch syndrome, a hereditary disorder resulting from germline mutations in mismatch repair (MMR) genes ( 2 ). Most pituitary carcinomas arise from functioning corticotroph or lactotroph lineages, and their clinical management remains challenging ( 1 ). Temozolomide is the recommended first?line…
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