Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. Export

@article{citeulike:3097049, abstract = {PURPOSE: To investigate the prognostic value of tumor-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in hepatocellular carcinoma (HCC) patients after resection. PATIENTS AND METHODS: CD3+, CD4+, CD8+, Foxp3-positive, and granzyme B-positive TILs were assessed by immunohistochemistry in tissue microarrays containing HCC from 302 patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff. RESULTS: CD3+, CD4+, CD8+ TILs were associated with neither overall survival (OS) nor disease-free survival (DFS). The presence of low intratumoral Tregs in combination with high intratumoral activated CD8+ cytotoxic cells (CTLs), a balance toward CTLs, was an independent prognostic factor for both improved DFS (P = .001) and OS (P < .0001). Five-year OS and DFS rates were only 24.1\% and 19.8\% for the group with intratumoral high Tregs and low activated CTLs, compared with 64.0\% and 59.4\% for the group with intratumoral low Tregs and high activated CTLs, respectively. Either intratumoral Tregs alone (P = .001) or intratumoral activated CTLs (P = .001) alone is also an independent predictor for OS. In addition, high Tregs density was associated with both absence of tumor encapsulation (P = .032) and presence of tumor vascular invasion (P = .031). CONCLUSION: Tregs are associated with HCC invasiveness, and intratumoral balance of regulatory and cytotoxic T cells is a promising independent predictor for recurrence and survival in HCC. A combination of depletion of Tregs and concomitant stimulation of effector T cells may be an effective immunotherapy to reduce recurrence and prolong survival after surgery.}, address = {Liver Cancer Institute, Zhong Shan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis \& Cancer Invasion, the Chinese Ministry of Education, Shanghai, People's Republic of China.}, author = {Gao, Q. and Qiu, S. J. and Fan, J. and Zhou, J. and Wang, X. Y. and Xiao, Y. S. and Xu, Y. and Li, Y. W. and Tang, Z. Y.}, citeulike-article-id = {3097049}, citeulike-linkout-0 = {http://dx.doi.org/10.1200/JCO.2006.09.4565}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17577038}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17577038}, day = {20}, doi = {10.1200/JCO.2006.09.4565}, issn = {1527-7755}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, keywords = {cd8\_t\_cell, hepatocellular\_carcinoma, treg}, month = {June}, number = {18}, pages = {2586--2593}, posted-at = {2008-08-07 22:30:47}, priority = {2}, title = {Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection.}, url = {http://dx.doi.org/10.1200/JCO.2006.09.4565}, volume = {25}, year = {2007} }

TY - JOUR ID - citeulike:3097049 L3 - citeulike-article-id:3097049 N2 - PURPOSE: To investigate the prognostic value of tumor-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in hepatocellular carcinoma (HCC) patients after resection. PATIENTS AND METHODS: CD3+, CD4+, CD8+, Foxp3-positive, and granzyme B-positive TILs were assessed by immunohistochemistry in tissue microarrays containing HCC from 302 patients. Prognostic effects of low- or high-density TIL subsets were evaluated by Cox regression and Kaplan-Meier analysis using median values as cutoff. RESULTS: CD3+, CD4+, CD8+ TILs were associated with neither overall survival (OS) nor disease-free survival (DFS). The presence of low intratumoral Tregs in combination with high intratumoral activated CD8+ cytotoxic cells (CTLs), a balance toward CTLs, was an independent prognostic factor for both improved DFS (P = .001) and OS (P < .0001). Five-year OS and DFS rates were only 24.1% and 19.8% for the group with intratumoral high Tregs and low activated CTLs, compared with 64.0% and 59.4% for the group with intratumoral low Tregs and high activated CTLs, respectively. Either intratumoral Tregs alone (P = .001) or intratumoral activated CTLs (P = .001) alone is also an independent predictor for OS. In addition, high Tregs density was associated with both absence of tumor encapsulation (P = .032) and presence of tumor vascular invasion (P = .031). CONCLUSION: Tregs are associated with HCC invasiveness, and intratumoral balance of regulatory and cytotoxic T cells is a promising independent predictor for recurrence and survival in HCC. A combination of depletion of Tregs and concomitant stimulation of effector T cells may be an effective immunotherapy to reduce recurrence and prolong survival after surgery. IS - 18 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology SN - 1527-7755 AD - Liver Cancer Institute, Zhong Shan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, the Chinese Ministry of Education, Shanghai, People's Republic of China. EP - 2593 TI - Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. VL - 25 SP - 2586 KW - cd8_t_cell KW - hepatocellular_carcinoma KW - treg AU - Gao, Q AU - Qiu, SJ AU - Fan, J AU - Zhou, J AU - Wang, XY AU - Xiao, YS AU - Xu, Y AU - Li, YW AU - Tang, ZY PY - 2007/06/20/ UR - http://dx.doi.org/10.1200/JCO.2006.09.4565 ER -