Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy: role of CD62L
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IMMUNOLOGY & MICROBIOLOGY IN MIAMI
Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy: role of CD62L C. Marcela Dı´az-Montero • Abdel-Aziz Zidan • Maria F. Pallin • Vasileios Anagnostopoulos • Mohamed L. Salem • Eric Wieder • Krishna Komanduri • Alberto J. Montero • Mathias G. Lichtenheld Mathias G. Lichtenheld
Ó Springer Science+Business Media New York 2013
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. Keywords
Adoptive immunotherapy CD8 T cells CD62L Cyclophosphamide Melanoma Pmel
Present Address: C. M. Dı´az-Montero Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA e-mail: [email protected] A.-A. Zidan M. L. Salem Department of Zoology, Tanta University, Tanta, Egypt
K. Komanduri Department of Medicine and Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA Present Address: A. J. Montero Department of Solid Oncology, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH, USA
M. F. Pallin M. G. Lichtenheld (&) Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA e-mail: [email protected] V. Anagnostopoulos E. Wieder Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA
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Immunology & Microbiology in Miami
Introduction Cancer immunotherapy has come a long way. Over 120 years ago, it began with the experimental injection of microbial toxins into sarcoma patients in New York [1]. Fast forward, in just the past
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