IL-7 is superior to IL-2 for ex vivo expansion of tumour-specific CD4(+) T cells.
It is well established that tumours hinder both natural and vaccine-induced tumour-specific CD4(+) T-cell responses. Adoptive T-cell therapy has the potential to circumvent functional tolerance and enhance anti-tumour protective responses. While protocols suitable for the expansion of cytotoxic CD8(+) T cells are currently available, data on tumour-specific CD4(+) T cells remain scarce. We report here that CD4(+) T cells sensitized to tumour-associated Ag in vivo, proliferate in vitro in response to IL-7 without the need for exogenous Ag stimulation and accumulate several folds while preserving a memory-like phenotype. Both cell proliferation and survival accounts for the outgrowth of tumour-sensitized T cells among other memory and naive lymphocytes following exposure to IL-7. Also IL-2, previously used to expand anti-tumour CTL, promotes tumour-specific CD4(+) T-cell accumulation. However, IL-7 is superior to IL-2 at preserving lymphocyte viability, in vitro and in vivo, maintaining those properties, that are required by helper CD4(+) T cells to confer therapeutic efficacy upon transplantation in tumour-bearing hosts. Together our data support a unique role for IL-7 in retrieving memory-like CD4(+) T cells suitable for adoptive T-cell therapy.
Caserta
Stefano
S
Program in Immunology and Bio-Immuno-gene therapy of Cancer (PIBIC), Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
Alessi
Patrizia
P
Basso
Veronica
V
Mondino
Anna
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D016219:Immunotherapy, Adoptive; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy
D019409:Interleukin-15; D007376:Interleukin-2; D015850:Interleukin-6; D015851:Interleukin-7