Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy: Role of CD62L

C. Marcela Díaz-Montero, Abdel Aziz Zidan, Maria F. Pallin, Vasileios Anagnostopoulos, Mohamed L. Salem, Eric Wieder, Krishna V Komanduri, Alberto J. Montero, Mathias G Lichtenheld

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

CD62L governs the circulation of CD8+ T cells between lymph nodes and peripheral tissues, whereby the expression of CD62L by CD8+ T cells promotes their recirculation through lymph nodes. As such, CD62L participates in the fate of adoptively transferred CD8+ T cells and may control their effectiveness for cancer immunotherapy, including settings in which host preconditioning results in the acute lymphopenia-induced proliferation of the transferred cells. Indeed, previous studies correlated CD62L expression by donor CD8+ cells with the success rate of adoptive cell therapy (ACT). Here, we analyzed the functions and fate of ex vivo-activated, tumor-specific CD62L-/- CD8+ T cells in a mouse melanoma model for ACT. Unexpectedly, we observed that CD62L-/- CD8+ T cells were functionally indistinguishable from CD62L +/+ CD8+ T cells, i.e., both greatly expanded in cyclophosphamide preconditioned animals, controlled subcutaneously and hematogenously spreading tumors, and generated anti-tumor-specific CD8 + T cell memory. Moreover, even in hosts with rudimentary secondary lymphoid organs (LT-/- animals), CD8+ T cells with and without CD62L expanded equivalently to those adoptively transferred into wild-type animals these results put into question the utility of CD62L as a predictive biomarker for the efficacy of ex vivo-expanded T cells after ACT in lymphopenic conditions and also offer new insights into the homing, engraftment, and memory generation of adoptively transferred ex vivo-activated CD8 + T cells.

Original languageEnglish
Pages (from-to)23-33
Number of pages11
JournalImmunologic Research
Volume57
Issue number1-3
DOIs
StatePublished - Dec 1 2013

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Keywords

  • Adoptive immunotherapy
  • CD62L
  • CD8 T cells
  • Cyclophosphamide
  • Melanoma
  • Pmel

ASJC Scopus subject areas

  • Immunology

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