Functional T cell responses to tumor antigens in breast cancer patients have a distinct phenotype and cytokine signature.
The overall prevalence with which endogenous tumor Ags induce host T cell responses is unclear. Even when such responses are detected, they do not usually result in spontaneous remission of the cancer. We hypothesized that this might be associated with a predominant phenotype and/or cytokine profile of tumor-specific responses that is different from protective T cell responses to other chronic Ags, such as CMV. We detected significant T cell responses to CEA, HER-2/neu, and/or MAGE-A3 in 17 of 21 breast cancer patients naive to immunotherapy. The pattern of T cell cytokines produced in response to tumor-associated Ags (TAAs) in breast cancer patients was significantly different from that produced in response to CMV or influenza in the same patients. Specifically, there was a higher proportion of IL-2-producing CD8(+) T cells, and a lower proportion of IFN-gamma-producing CD4(+) and/or CD8(+) T cells responding to TAAs compared with CMV or influenza Ags. Finally, the phenotype of TAA-responsive CD8(+) T cells in breast cancer patients was almost completely CD28(+)CD45RA(-) (memory phenotype). CMV-responsive CD8(+) T cells in the same patients were broadly distributed among phenotypes, and contained a high proportion of terminal effector cells (CD27(-)CD28(-)CD45RA(+)) that were absent in the TAA responses. Taken together, these results suggest that TAA-responsive T cells are induced in breast cancer patients, but those T cells are phenotypically and functionally different from CMV- or influenza-responsive T cells. Immunotherapies directed against TAAs may need to alter these T cell signatures to be effective.
Inokuma
Margaret
M
BD Biosciences, San Jose, CA 95131, USA.
dela Rosa
Corazon
C
Schmitt
Charles
C
Haaland
Perry
P
Siebert
Janet
J
Petry
Douglas
D
Tang
Mengxiang
M
Suni
Maria A
MA
Ghanekar
Smita A
SA
Gladding
Daiva
D
Dunne
John F
JF
Maino
Vernon C
VC
Disis
Mary L
ML
Maecker
Holden T
HT
D000328:Adult; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007251:Influenza, Human / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D016207:Cytokines