التفاصيل البيبلوغرافية
| العنوان: |
Intracellular accumulation of PD-1 molecules in circulating T lymphocytes in advanced malignant melanoma: an implication for immune evasion mechanism. |
| المؤلفون: |
Takahashi, Ryo1 (AUTHOR), Sato, Yohei2 (AUTHOR), Kimishima, Momoko2 (AUTHOR), Shiohara, Tetsuo1,2 (AUTHOR), Ohyama, Manabu1,2 (AUTHOR) manabuohy@ks.kyorin-u.ac.jp |
| المصدر: |
International Journal of Clinical Oncology. Oct2020, Vol. 25 Issue 10, p1861-1869. 9p. |
| مصطلحات موضوعية: |
*PROGRAMMED cell death 1 receptors, *T cells, *MELANOMA, *CELL membranes, *MOLECULES |
| مستخلص: |
Background: The blockade of cell surface PD-1 ((sur)PD-1) by monoclonal antibodies, represented by nivolumab, provides the strategy to treat advanced malignant melanoma (AMM). The intracellular presence of PD-1 molecules have been reported in some T cell subsets, however, their kinetic association with those expressed on the cell surface, let alone their significance in antitumor immunity has been ill-investigated. Methods: Intracellular PD-1 expression status in T cell subsets in AMM cases during nivolumab administration was chronologically characterized. The kinetics of PD-1 molecules within AMM-derived T cells was assessed in vitro in conjunction with their functional properties. Results: Increase in (sur)PD-1 and intracellular PD-1 ((int)PD-1+) expression was characteristic for AMM T cells. After short-term culture, virtually (sur)PD-1– nivolumab-treated AMM T cells restore (sur)PD-1 expression, which could not be explained by the detachment of nivolumab from PD-1 epitopes alone. The blockade of trans-Golgi network resulted in the decrease in the extent of (sur)PD-1 recovery, suggesting the translocation of accumulated (int)PD-1 to the cell surface. Antigen-specific PD-1+ T cells significantly increased in (int)PD-1+ cells after treatment. In addition, a surge in (int)PD-1+CD4+ T cells was observed prior to the emergence of skin rash as an immune-related adverse event (irAE). Conclusions: Accumulated (int)PD-1 in T cells may contribute to enhanced immune evasion in AMM. Evaluation of intracellular PD-1 expression would be useful for better management of nivolumab-treated AMM patients in view of predicting treatment response and the incidence of irAE. Our findings further support the necessity of periodical administration of nivolumab for treating AMM. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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