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 Citations (Scopus)

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

Fingerprint

Cell- and Tissue-Based Therapy
T-Lymphocytes
Neoplasms
Lymph Nodes
Animal Structures
Lymphopenia
Wild Animals
Immunotherapy
Cyclophosphamide
Melanoma
Biomarkers
Cell Proliferation

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy : Role of CD62L. / Díaz-Montero, C. Marcela; Zidan, Abdel Aziz; Pallin, Maria F.; Anagnostopoulos, Vasileios; Salem, Mohamed L.; Wieder, Eric; Komanduri, Krishna V; Montero, Alberto J.; Lichtenheld, Mathias G.

In: Immunologic Research, Vol. 57, No. 1-3, 01.12.2013, p. 23-33.

Research output: Contribution to journalArticle

Díaz-Montero, C. Marcela ; Zidan, Abdel Aziz ; Pallin, Maria F. ; Anagnostopoulos, Vasileios ; Salem, Mohamed L. ; Wieder, Eric ; Komanduri, Krishna V ; Montero, Alberto J. ; Lichtenheld, Mathias G. / Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy : Role of CD62L. In: Immunologic Research. 2013 ; Vol. 57, No. 1-3. pp. 23-33.
@article{133ef1e41970428ead3c8f6e400ec055,
title = "Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy: Role of CD62L",
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, CD62L, CD8 T cells, Cyclophosphamide, Melanoma, Pmel",
author = "D{\'i}az-Montero, {C. Marcela} and Zidan, {Abdel Aziz} and Pallin, {Maria F.} and Vasileios Anagnostopoulos and Salem, {Mohamed L.} and Eric Wieder and Komanduri, {Krishna V} and Montero, {Alberto J.} and Lichtenheld, {Mathias G}",
year = "2013",
month = "12",
day = "1",
doi = "10.1007/s12026-013-8456-1",
language = "English",
volume = "57",
pages = "23--33",
journal = "Immunologic Research",
issn = "0257-277X",
publisher = "Humana Press",
number = "1-3",

}

TY - JOUR

T1 - Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy

T2 - Role of CD62L

AU - Díaz-Montero, C. Marcela

AU - Zidan, Abdel Aziz

AU - Pallin, Maria F.

AU - Anagnostopoulos, Vasileios

AU - Salem, Mohamed L.

AU - Wieder, Eric

AU - Komanduri, Krishna V

AU - Montero, Alberto J.

AU - Lichtenheld, Mathias G

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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.

AB - 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.

KW - Adoptive immunotherapy

KW - CD62L

KW - CD8 T cells

KW - Cyclophosphamide

KW - Melanoma

KW - Pmel

UR - http://www.scopus.com/inward/record.url?scp=84891495309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891495309&partnerID=8YFLogxK

U2 - 10.1007/s12026-013-8456-1

DO - 10.1007/s12026-013-8456-1

M3 - Article

C2 - 24218360

AN - SCOPUS:84891495309

VL - 57

SP - 23

EP - 33

JO - Immunologic Research

JF - Immunologic Research

SN - 0257-277X

IS - 1-3

ER -