title: Analyses of T cell-mediated immune response to a human melanoma-associated antigen by the young and the elderly.
abstract: Elderly cancer patients are often excluded from immune-based clinical trials and therapies based on the belief that they respond poorly to tumor antigens. Using melanoma as a model and melanoma related Mart-127-35 epitope specific T cell receptor (TCR) engineered T cells as a tool we compared the T cell responses from young and elderly to the Mart-127-35 epitope, ex vivo. We also compared the natural Treg (nTreg) activities and the expression of a number of genes associated with immune response by quantitative real-time reverse Transcription Polymerase Chain Reaction (qRTPCR) in formalin fixed primary melanomas, in situ. We detected a significant difference in CD8(+) T cell response to Flu antigen (influenza matrix peptide Flu MP58-66), but the responses of the two cohorts to melanoma antigen were comparable. nTreg activities in the elderly was significantly compromised. The qPCR analyses of tissues from elderly patients revealed lower levels of Fox-P3 expression but comparable levels of expression of IL-2, IFNγ, TNFα, IL-4, IL-10, IDO, and TGFβ. These findings indicate that elderly patients might be capable of responding to tumor antigens, and need not be excluded from immune-based therapies or clinical trials.
authors: Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, CT 06030-1628, USA. chakraborty@uchc.edu
authors: Nitya G
authors: NG
authors: Chakraborty
authors: Meeta
authors: M
authors: Yadav
authors: Soheil S
authors: SS
authors: Dadras
authors: Prashant
authors: P
authors: Singh
authors: Arvind
authors: A
authors: Chhabra
authors: Richard
authors: R
authors: Feinn
authors: Phillip E
authors: PE
authors: Kerr
authors: Jane M
authors: JM
authors: Grant-Kels
authors: Bijay
authors: B
authors: Mukherji
authors: Upendra P
authors: UP
authors: Hegde
mesh_terms: D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D058965:MART-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D058950:Melanoma-Specific Antigens / Q000276:immunology*; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D053645:Interleukin-2 Receptor alpha Subunit; D058965:MART-1 Antigen; D058950:Melanoma-Specific Antigens; D011948:Receptors, Antigen, T-Cell