Frontiers in immunology · 2026
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.
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Sugiyama Mariko, Iwama Shintaro, Takeuchi Kazuhito, Kobayashi Tomoko, Murase Takanori, Hagiwara Daisuke, Chen Hao, Nagata Yuichi, Saito Ryuta, Akatsuka Yoshiki, Arima Hiroshi
Аннотация
CONTEXT: 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.
OBJECTIVE: To evaluate tumor-infiltrating lymphocytes (TILs) in pituitary carcinoma and to compare T-cell receptor (TCR) clonotypes between the pituitary and peripheral blood.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVE: To evaluate tumor-infiltrating lymphocytes (TILs) in pituitary carcinoma and to compare T-cell receptor (TCR) clonotypes between the pituitary and peripheral blood.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.