PURPOSE: To study the effect of autologous tumor cell vaccinations on the presence and numbers of circulating CD8+ T cells specific for tumor-associated antigens (TAA) in metastatic melanoma patients. To investigate the correlation between the presence of tumor-infiltrating lymphocytes (TIL) and circulating TAA-specific CD8+ T cells before and after autologous tumor cell vaccination with overall survival. EXPERIMENTAL DESIGN: Twenty-five stage III and resected stage IV metastatic melanoma patients were adjuvantly treated with a series of intracutaneously injected autologous tumor cell vaccinations, of which the first two contained BCG as an immunostimulatory adjuvant. Tumor samples and blood samples obtained before and after vaccination of these patients were studied for the presence of TAA-specific T cells using HLA-tetramers and results were correlated with survival. RESULTS: In 5 of 17 (29%) melanoma patients, circulating TAA-specific T cells were detectable prior to immunizations. No significant changes in the frequency and specificity were found during the treatment period in all patients. Presence of circulating TAA-specific T cells was not correlated with survival (log rank, P=0.215). Inside melanoma tissue, TAA-specific TIL could be detected in 75% of 16 available tumor samples. In case of detectable TAA-specific TIL, median survival was 22.5 months compared to median survival of 4.5 months in case of absence of TAA-specific T cells (log rank, P=0.0094). In none of the patients, TAA-specific T cells were found both in tumor tissue and blood at the same time. CONCLUSIONS: These data suggest that the presence of TAA-specific TILs forms a prognostic factor, predicting improved survival in advanced-stage melanoma patients. The absence of TAA-specific T cells in the circulation suggests that homing of the tumor-specific T cell population to the tumor site contributes to the effectiveness of antitumor immunity.
PURPOSE: To study the effect of autologous tumor cell vaccinations on the presence and numbers of circulating CD8+ T cells specific for tumor-associated antigens (TAA) in metastatic melanomapatients. To investigate the correlation between the presence of tumor-infiltrating lymphocytes (TIL) and circulating TAA-specific CD8+ T cells before and after autologous tumor cell vaccination with overall survival. EXPERIMENTAL DESIGN: Twenty-five stage III and resected stage IV metastatic melanomapatients were adjuvantly treated with a series of intracutaneously injected autologous tumor cell vaccinations, of which the first two contained BCG as an immunostimulatory adjuvant. Tumor samples and blood samples obtained before and after vaccination of these patients were studied for the presence of TAA-specific T cells using HLA-tetramers and results were correlated with survival. RESULTS: In 5 of 17 (29%) melanomapatients, circulating TAA-specific T cells were detectable prior to immunizations. No significant changes in the frequency and specificity were found during the treatment period in all patients. Presence of circulating TAA-specific T cells was not correlated with survival (log rank, P=0.215). Inside melanoma tissue, TAA-specific TIL could be detected in 75% of 16 available tumor samples. In case of detectable TAA-specific TIL, median survival was 22.5 months compared to median survival of 4.5 months in case of absence of TAA-specific T cells (log rank, P=0.0094). In none of the patients, TAA-specific T cells were found both in tumor tissue and blood at the same time. CONCLUSIONS: These data suggest that the presence of TAA-specific TILs forms a prognostic factor, predicting improved survival in advanced-stage melanomapatients. The absence of TAA-specific T cells in the circulation suggests that homing of the tumor-specific T cell population to the tumor site contributes to the effectiveness of antitumor immunity.
Authors: Gregory T Wolf; Willard E Fee; Robert W Dolan; Jeffrey S Moyer; Michael J Kaplan; Paul M Spring; James Suen; Daniel E Kenady; Jason G Newman; William R Carroll; M Boyd Gillespie; Scott M Freeman; Lorraine Baltzer; Terry D Kirkley; Harvey J Brandwein; John W Hadden Journal: Head Neck Date: 2011-01-31 Impact factor: 3.147
Authors: Xi Zhao; Anamika Bose; Hideo Komita; Jennifer L Taylor; Nina Chi; Devin B Lowe; Hideho Okada; Ying Cao; Debabrata Mukhopadhyay; Peter A Cohen; Walter J Storkus Journal: J Immunol Date: 2012-01-13 Impact factor: 5.422
Authors: Vijaya B Joshi; Sean M Geary; Brett P Gross; Amaraporn Wongrakpanich; Lyse A Norian; Aliasger K Salem Journal: Expert Rev Vaccines Date: 2014-01 Impact factor: 5.217
Authors: Peter W Chen; Jessamee K Mellon; Elizabeth Mayhew; Shixuan Wang; Yu Guang He; Nick Hogan; Jerry Y Niederkorn Journal: Exp Eye Res Date: 2007-07-25 Impact factor: 3.467
Authors: Paulo Cesar Maciag; Matthew M Seavey; Zhen-Kun Pan; Soldano Ferrone; Yvonne Paterson Journal: Cancer Res Date: 2008-10-01 Impact factor: 12.701