Absence of amplification of CD4+CD25(high) regulatory T cells during in vitro expansion of tumor-infiltrating lymphocytes in melanoma patients.
The exact role of CD4+CD25(high) regulatory T cells (Treg) in adoptive immunotherapy of melanoma is still to be determined, and an association between an expansion of Treg cells and the expansion of therapeutic tumor-infiltrating lymphocytes (TIL) remains unelucidated. In this context, the aim of our study was to determine whether functional Treg cells were detectable and amplified among in vitro-expanded TIL from 10 metastatic melanoma lymph nodes (LNs). In this study, we investigated the expression of forkhead/winged helix transcription factor 3 (Foxp3) in melanoma-invaded LNs and determined proportion and functionality of Treg cells among TIL extracted from these 10 metastatic melanoma LNs at different steps of their in vitro expansion. We found that metastatic melanoma LNs expressed very heterogeneous levels of Foxp3 and that CD4+CD25(high) Treg cells extracted from these LNs were detectable at each step of the in vitro culture of TIL but decreasing during the culture. In addition, functional assays demonstrated that these CD4+CD25(high) T cells were capable of suppressing autologous CD8+ and CD4+CD25- T cell proliferation. These cells were indeed Treg cells as they expressed Foxp3. In conclusion, our work suggests that CD4+CD25(high) Foxp3 expressing T cells are not expanded during in vitro amplification of TIL obtained from melanoma-invaded LNs.
Knol
Anne Chantal
AC
INSERM, U601, 9 Quai Moncousu Nantes Cedex 01, France.
Lemaître
Fabrice
F
Pandolfino
Marie Christine
MC
Volteau
Christelle
C
Quéreux
Gaëlle
G
Saiagh
Soraya
S
Khammari
Amir
A
Viguier
Manuelle
M
Dréno
Brigette
B
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit