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Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer

BACKGROUND: Neoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alteratio...

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Autores principales: Liang, Yun, Lü, Weiguo, Zhang, Xiaofei, Lü, Bingjian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260654/
https://www.ncbi.nlm.nih.gov/pubmed/30474571
http://dx.doi.org/10.1186/s13000-018-0770-4
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author Liang, Yun
Lü, Weiguo
Zhang, Xiaofei
Lü, Bingjian
author_facet Liang, Yun
Lü, Weiguo
Zhang, Xiaofei
Lü, Bingjian
author_sort Liang, Yun
collection PubMed
description BACKGROUND: Neoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alterations of tumor infiltrating lymphocytes (TILs) before and after NACT and analyzed their prognostic significance in advanced cervical cancer patients treated with platinum-based NACT. METHODS: We recruited 137 patients with stage Ib2 and IIa2 cervical cancer retrospectively. Pretreatment biopsy and surgical specimens after NACT were immunostained with CD8 and Foxp3. The densities of intratumoral and peritumoral immunopositive TILs were analyzed separately. RESULTS: Foxp3+ T cells density significantly decreased in both intratumoral (median 28.49 vs. 19.97; Z = − 8.635, p < 0.001) and peritumoral (median 113.53 vs. 82.48; Z = − 3.741, p < 0.001) areas after NACT, whereas CD8+ T cell counts remained stable in both intratumoral (median 121.32 vs. 109.59; Z = − 0.817,p = 0.414) and peritumoral (median 402.56 vs. 390.84; Z = − 1.138,p = 0.255) areas. Patients with pathological complete response (pCR) had significantly lower number of Foxp3+ T cell density after NACT than non-pCR cases in both intratumoral (median16.12 vs. 22.00; Z = − 2.009, p = 0.045) and peritumoral areas(median 63.31 vs. 98.48; Z = − 2.469, p = 0.014). Multivariate analyses demonstrated that high ratio of intratumoral CD8/peritumoral Foxp3 in residual tumors was independent prognostic factor for both progression-free survival (HR = 0.297; 95% CI, 0.109–0.810, p = 0.018) and overall survival (HR = 0.078; 95% CI, 0.010–0.598, p = 0.014). CONCLUSIONS: NACT in cervical cancers can induce anti-cancer immunity by altering TILs subsets. An elevated intratumoral CD8/peritumoral Foxp3 ratio after NACT may confer a favorable clinical outcome.
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spelling pubmed-62606542018-11-30 Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer Liang, Yun Lü, Weiguo Zhang, Xiaofei Lü, Bingjian Diagn Pathol Research BACKGROUND: Neoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alterations of tumor infiltrating lymphocytes (TILs) before and after NACT and analyzed their prognostic significance in advanced cervical cancer patients treated with platinum-based NACT. METHODS: We recruited 137 patients with stage Ib2 and IIa2 cervical cancer retrospectively. Pretreatment biopsy and surgical specimens after NACT were immunostained with CD8 and Foxp3. The densities of intratumoral and peritumoral immunopositive TILs were analyzed separately. RESULTS: Foxp3+ T cells density significantly decreased in both intratumoral (median 28.49 vs. 19.97; Z = − 8.635, p < 0.001) and peritumoral (median 113.53 vs. 82.48; Z = − 3.741, p < 0.001) areas after NACT, whereas CD8+ T cell counts remained stable in both intratumoral (median 121.32 vs. 109.59; Z = − 0.817,p = 0.414) and peritumoral (median 402.56 vs. 390.84; Z = − 1.138,p = 0.255) areas. Patients with pathological complete response (pCR) had significantly lower number of Foxp3+ T cell density after NACT than non-pCR cases in both intratumoral (median16.12 vs. 22.00; Z = − 2.009, p = 0.045) and peritumoral areas(median 63.31 vs. 98.48; Z = − 2.469, p = 0.014). Multivariate analyses demonstrated that high ratio of intratumoral CD8/peritumoral Foxp3 in residual tumors was independent prognostic factor for both progression-free survival (HR = 0.297; 95% CI, 0.109–0.810, p = 0.018) and overall survival (HR = 0.078; 95% CI, 0.010–0.598, p = 0.014). CONCLUSIONS: NACT in cervical cancers can induce anti-cancer immunity by altering TILs subsets. An elevated intratumoral CD8/peritumoral Foxp3 ratio after NACT may confer a favorable clinical outcome. BioMed Central 2018-11-24 /pmc/articles/PMC6260654/ /pubmed/30474571 http://dx.doi.org/10.1186/s13000-018-0770-4 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Liang, Yun
Lü, Weiguo
Zhang, Xiaofei
Lü, Bingjian
Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer
title Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer
title_full Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer
title_fullStr Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer
title_full_unstemmed Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer
title_short Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer
title_sort tumor-infiltrating cd8+ and foxp3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260654/
https://www.ncbi.nlm.nih.gov/pubmed/30474571
http://dx.doi.org/10.1186/s13000-018-0770-4
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