Marked anti-tumor effects of CD8(+)CD62L(+) T cells from melanoma-bearing mice

Immunol Invest. 2015;44(2):147-63. doi: 10.3109/08820139.2014.944980. Epub 2014 Aug 14.

Abstract

CD8(+)CD62L(+) T cells have been shown to play pivotal roles in anti-viral immunity, chronic myeloid leukemia and renal cell carcinoma. Recently, CD8(+)CD62L(+) T cells from naïve mice (nCD8(+)CD62L(+) T cells) have shown superior anti-tumor properties in melanoma-bearing mice. Considering that antigen-specific memory T cells have shown to possess more potent immunity than non-specific memory T cells, we hypothesized that CD8(+)CD62L(+) T cells from tumor-bearing individuals (mCD8(+)CD62L(+) T cells) might have superior anti-tumor effect than nCD8(+)CD62L(+) T cells. Therefore, we investigated phenotypes, functions and the in vivo distribution of mCD8(+)CD62L(+) T cells in tumor-bearing mice. We found that, while keeping the features of central memory T cells, the frequency of mCD8(+)CD62L(+) T cell in the spleen of tumor-bearing mice was significantly higher than that the one of nCD8(+)CD62L(+) T cell in naive mice. Moreover, we demonstrated that mCD8(+)CD62L(+) T cells had higher proliferation rate and IFN-γ production than nCD8(+)CD62L(+) T cells, in vitro. We performed adoptive transfer of mCD8(+)CD62L(+) T cells into melanoma-bearing mice and tracked them in spleen, lymph nodes and in melanoma tissues. Our results show that mCD8(+)CD62L(+) T cells had stronger in vivo anti-tumoral activity than nCD8(+)CD62L(+) T cells. This study highlights the therapeutic potential of mCD8(+)CD62L(+) T cells in the immunotherapy of melanoma and possibly other tumors.

Keywords: Anti-tumor immunity; CD8+CD62L+ T cells; T subtypes; melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / metabolism
  • Apoptosis / immunology
  • Biomarkers
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Disease Models, Animal
  • Female
  • Immunophenotyping
  • Immunotherapy, Adoptive
  • Interferon-gamma / biosynthesis
  • L-Selectin / metabolism*
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Melanoma / immunology*
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Melanoma / therapy
  • Mice
  • Phenotype
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Antigens, Surface
  • Biomarkers
  • L-Selectin
  • Interferon-gamma