Comparative assessment of TCRBV diversity in T lymphocytes present in blood, metastatic lesions, and DTH sites of two melanoma patients vaccinated with an IL-7 gene-modified autologous tumor cell vaccine.
A phase I clinical trial using autologous, IL-7 gene-modified tumor cells in patients with disseminated melanoma has been recently completed. Although no major clinical responses were observed, increased antitumor cytotoxicity was measured in postvaccine peripheral blood lymphocytes in a subset of treated patients. To analyze the in situ immune response, the T cell receptor beta-chain variable region (BV) repertoire of T cells infiltrating postvaccine lesions was studied in two patients, and compared with that of T cells present in prevaccine ones, in peripheral blood lymphocytes, and, in one patient, in delayed type hypersensitivity (DTH) sites of autologous melanoma inoculum. A relative expansion of T cells expressing few BVs was observed in all postvaccine metastases, and their intratumoral presence was confirmed by immunohistochemistry. Length pattern analysis of the complementarity determining region 3 (CDR3) indicated that the repertoire of T cells expressing some of these BVs was heterogeneous. At difference, CDR3, beta-chain joining region usage, and sequence analysis enabled us to demonstrate, within a T-cell subpopulation commonly expanded at DTH sites and at the postvaccine lesion of patient 1, that both DTH sites contained identical dominant T-cell clonotypes. One of them was also expressed at increased relative frequency in the postvaccine lesion compared to prevaccine specimens. These results provide evidence for immunological changes, including in situ clonally expanded T cells, in metastases of patients vaccinated with IL-7 gene-transduced cells.
Carsana
Marilisa
M
Human Tumor Immunobiology Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Tragni
Gabrina
G
Nicolini
Gabriella
G
Bersani
Ilaria
I
Parmiani
Giorgio
G
Anichini
Andrea
A
Sun
Yuan Sheng
YS
Möller
Peter
P
Schadendorf
Dirk
D
Sensi
Maria Luisa
ML
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007124:Immunoenzyme Techniques; D015851:Interleukin-7 / Q000235:genetics*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008545:Melanoma / Q000628:therapy*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012878:Skin Neoplasms / Q000628:therapy*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology; D014611:Vaccination
D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D019496:Cancer Vaccines; C109399:Cdr3 protein, Candida albicans; D017931:DNA Primers; D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta