Implications of Aging and Self-Tolerance on the Generation of Immune and Antitumor Immune Responses Export

@article{citeulike:4115540, abstract = {Cancer statistics show a disproportionately higher burden of tumors in the old. Most of the studies evaluating vaccination strategies have not taken into consideration the effect that aging has on the immune system. For the first time, we describe an animal tumor model in which self-tolerance and aging are present at the same time. FVB-Her-2/neu mice which are tolerant to neu antigens crossed with HLA-A2/Kb mice (A2xneu) develop spontaneous tumors when they are more than 22 months old. Analysis of CD8+ T-cell-specific responses in A2xneu mice indicated that the priming activity of old A2xneu mice to induce an immune response was diminished compared with young animals. Following intratumoral injections of CpG-ODN, [\~{}]30\% of young A2xneu mice rejected the tumor; however, no antitumor effect was observed in old A2xneu mice. Analysis of T regulatory cells (Treg) indicated that there are significantly more Tregs in old animals. After CpG-ODN vaccination plus Treg depletion, 70\% of young A2xneu mice rejected the tumor. The same treatment prolonged survival in old A2xneu mice, but none of the animals rejected the tumor. Even though CpG-ODN injections plus Treg depletion could rescue the antitumor responses against self-tumor antigens in young tolerant mice, the same therapy is not as effective in old tolerant hosts. Relevant tumor models such as the A2xneu mice in which self-tolerance and aging are present at the same time are critical to allow the optimization of vaccination strategies to effectively stimulate immune responses against self-tumor antigens in the young and the old. [Cancer Res 2008;68(13):5423-31] 10.1158/0008-5472.CAN-07-6436}, author = {Dominguez, Ana L. and Lustgarten, Joseph}, citeulike-article-id = {4115540}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-07-6436}, citeulike-linkout-1 = {http://cancerres.aacrjournals.org/cgi/content/abstract/68/13/5423}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18593945}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18593945}, comment = {More Tregs in the old.}, day = {1}, doi = {10.1158/0008-5472.CAN-07-6436}, journal = {Cancer Res}, keywords = {age, ageing, confounder, dod, immunosenescence, superlist, thelist, tolerance, treg}, month = {July}, number = {13}, pages = {5423--5431}, posted-at = {2009-02-28 17:00:49}, priority = {2}, title = {Implications of Aging and Self-Tolerance on the Generation of Immune and Antitumor Immune Responses}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-07-6436}, volume = {68}, year = {2008} }

TY - JOUR ID - citeulike:4115540 L3 - citeulike-article-id:4115540 N2 - Cancer statistics show a disproportionately higher burden of tumors in the old. Most of the studies evaluating vaccination strategies have not taken into consideration the effect that aging has on the immune system. For the first time, we describe an animal tumor model in which self-tolerance and aging are present at the same time. FVB-Her-2/neu mice which are tolerant to neu antigens crossed with HLA-A2/Kb mice (A2xneu) develop spontaneous tumors when they are more than 22 months old. Analysis of CD8+ T-cell-specific responses in A2xneu mice indicated that the priming activity of old A2xneu mice to induce an immune response was diminished compared with young animals. Following intratumoral injections of CpG-ODN, [~]30% of young A2xneu mice rejected the tumor; however, no antitumor effect was observed in old A2xneu mice. Analysis of T regulatory cells (Treg) indicated that there are significantly more Tregs in old animals. After CpG-ODN vaccination plus Treg depletion, 70% of young A2xneu mice rejected the tumor. The same treatment prolonged survival in old A2xneu mice, but none of the animals rejected the tumor. Even though CpG-ODN injections plus Treg depletion could rescue the antitumor responses against self-tumor antigens in young tolerant mice, the same therapy is not as effective in old tolerant hosts. Relevant tumor models such as the A2xneu mice in which self-tolerance and aging are present at the same time are critical to allow the optimization of vaccination strategies to effectively stimulate immune responses against self-tumor antigens in the young and the old. [Cancer Res 2008;68(13):5423-31] 10.1158/0008-5472.CAN-07-6436 IS - 13 JF - Cancer Res EP - 5431 TI - Implications of Aging and Self-Tolerance on the Generation of Immune and Antitumor Immune Responses VL - 68 SP - 5423 KW - age KW - ageing KW - confounder KW - dod KW - immunosenescence KW - superlist KW - thelist KW - tolerance KW - treg N1 - More Tregs in the old. AU - Dominguez, Ana AU - Lustgarten, Joseph PY - 2008/07/01/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-07-6436 ER -