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 language | English |
|---|---|
| Pages (from-to) | 23-33 |
| Number of pages | 11 |
| Journal | Immunologic Research |
| Volume | 57 |
| Issue number | 1-3 |
| DOIs | |
| State | Published - Dec 1 2013 |
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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 journal › Article
}
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 -