Adoptive CD8+ T cell therapy generates immunological memory to inhibit melanoma metastasis

Jinfei Fu, Anze Yu, Juyu Tang, Bin He, Wenhao Chen

Research output: Contribution to journalArticle

Abstract

Adoptive T cell therapy has emerged as a promising treatment for cancer. However, it is unknown whether adoptively transferred anti-tumor T cells can form immunological memory and provide continuous protection against cancer metastasis. Herein, we used TCR transgenic Pmel-1 CD8+ T cells as a model to investigate whether early transferred Pmel-1 CD8+ T cells can generate immunological memory to prevent later melanoma metastasis. Upon stimulation with the cognate melanoma-associated hgp100 antigen, in vitro cultured Pmel-1 CD8+ T cells developed into effector T (Teff) cells that exhibited potent cytotoxic activity against B16F10 melanoma cells. Next, B16F10 melanoma cells were intravenously injected into C57BL/6 (B6) mice to establish experimental lung metastasis. In vitro generated Pmel-1 Teff cells were adoptively transferred into the mice on the same day of or three weeks prior to B16F10 cell inoculation. We found that adoptive Pmel-1 Teff cell therapy significantly inhibited the B16F10 lung metastasis and prolonged the animal survival. Importantly, Pmel-1 Teff cells transferred three weeks prior to tumor inoculation were as potent as the Pmel-1 Teff cells transferred on the same day in inhibiting melanoma metastasis. Hence, our results suggest that adoptive CD8+ Teff cell therapy generates immunological memory that continuously protect against melanoma metastasis.

Original languageEnglish (US)
Pages (from-to)7262-7274
Number of pages13
JournalAmerican Journal of Translational Research
Volume12
Issue number11
StatePublished - 2020

Keywords

  • Adoptive cell therapy
  • B16 melanoma
  • CD8 T cell
  • Cancer metastasis
  • IVIS
  • Pmel-1

ASJC Scopus subject areas

  • Molecular Medicine
  • Clinical Biochemistry
  • Cancer Research

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