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Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance
BACKGROUND: The effects of neoadjuvant chemotherapy on immune markers remain largely unknown. The specific aim of this study was to assess stromal tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) protein expression in a cohort of breast cancer patients treated with neoadju...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547502/ https://www.ncbi.nlm.nih.gov/pubmed/28784153 http://dx.doi.org/10.1186/s13058-017-0884-8 |
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author | Pelekanou, Vasiliki Carvajal-Hausdorf, Daniel E. Altan, Mehmet Wasserman, Brad Carvajal-Hausdorf, Cristobal Wimberly, Hallie Brown, Jason Lannin, Donald Pusztai, Lajos Rimm, David L. |
author_facet | Pelekanou, Vasiliki Carvajal-Hausdorf, Daniel E. Altan, Mehmet Wasserman, Brad Carvajal-Hausdorf, Cristobal Wimberly, Hallie Brown, Jason Lannin, Donald Pusztai, Lajos Rimm, David L. |
author_sort | Pelekanou, Vasiliki |
collection | PubMed |
description | BACKGROUND: The effects of neoadjuvant chemotherapy on immune markers remain largely unknown. The specific aim of this study was to assess stromal tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) protein expression in a cohort of breast cancer patients treated with neoadjuvant chemotherapy. METHODS: Using quantitative immunofluorescence, we investigated stromal TILs and PD-L1 protein expression in pre-treatment and residual breast cancer tissue from a Yale Cancer Center patient cohort of 58 patients diagnosed with breast cancer from 2003 to 2009 and treated with neoadjuvant chemotherapy. We compared the TIL count and PD-L1 status in paired pre-treatment and residual cancer tissues and correlated changes and baseline levels with survival. RESULTS: Of the 58 patients, 46 (79.3%) had hormone-positive and 34 (58.6%) had node-positive breast cancer. Eighty-six percent of residual cancer tissues had TIL infiltration and 17% had PD-L1 expression. There was a trend for higher TIL counts in postchemotherapy compared to prechemotherapy samples (p = 0.09). Increase in TIL count was associated with longer 5-year recurrence-free survival (p = 0.02, HR = 3.9, 95% CI = 1.179–15.39). PD-L1 expression (both stromal and tumor cells) was significantly lower in post-treatment samples (p = 0.001). Change in PD-L1 expression after therapy or TILs and PD-L1 expression in the posttreatment samples did not correlate with survival. CONCLUSIONS: Increase in stromal TILs in residual cancer compared to pretreatment tissue is associated with improved recurrence-free survival. Despite a trend for increasing TIL counts, PD-L1 expression decreased in residual disease compared to pretreatment samples. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-017-0884-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5547502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-55475022017-08-09 Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance Pelekanou, Vasiliki Carvajal-Hausdorf, Daniel E. Altan, Mehmet Wasserman, Brad Carvajal-Hausdorf, Cristobal Wimberly, Hallie Brown, Jason Lannin, Donald Pusztai, Lajos Rimm, David L. Breast Cancer Res Research Article BACKGROUND: The effects of neoadjuvant chemotherapy on immune markers remain largely unknown. The specific aim of this study was to assess stromal tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) protein expression in a cohort of breast cancer patients treated with neoadjuvant chemotherapy. METHODS: Using quantitative immunofluorescence, we investigated stromal TILs and PD-L1 protein expression in pre-treatment and residual breast cancer tissue from a Yale Cancer Center patient cohort of 58 patients diagnosed with breast cancer from 2003 to 2009 and treated with neoadjuvant chemotherapy. We compared the TIL count and PD-L1 status in paired pre-treatment and residual cancer tissues and correlated changes and baseline levels with survival. RESULTS: Of the 58 patients, 46 (79.3%) had hormone-positive and 34 (58.6%) had node-positive breast cancer. Eighty-six percent of residual cancer tissues had TIL infiltration and 17% had PD-L1 expression. There was a trend for higher TIL counts in postchemotherapy compared to prechemotherapy samples (p = 0.09). Increase in TIL count was associated with longer 5-year recurrence-free survival (p = 0.02, HR = 3.9, 95% CI = 1.179–15.39). PD-L1 expression (both stromal and tumor cells) was significantly lower in post-treatment samples (p = 0.001). Change in PD-L1 expression after therapy or TILs and PD-L1 expression in the posttreatment samples did not correlate with survival. CONCLUSIONS: Increase in stromal TILs in residual cancer compared to pretreatment tissue is associated with improved recurrence-free survival. Despite a trend for increasing TIL counts, PD-L1 expression decreased in residual disease compared to pretreatment samples. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-017-0884-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-07 2017 /pmc/articles/PMC5547502/ /pubmed/28784153 http://dx.doi.org/10.1186/s13058-017-0884-8 Text en © The Author(s). 2017 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 Article Pelekanou, Vasiliki Carvajal-Hausdorf, Daniel E. Altan, Mehmet Wasserman, Brad Carvajal-Hausdorf, Cristobal Wimberly, Hallie Brown, Jason Lannin, Donald Pusztai, Lajos Rimm, David L. Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance |
title | Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance |
title_full | Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance |
title_fullStr | Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance |
title_full_unstemmed | Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance |
title_short | Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance |
title_sort | effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and pd-l1 expression in breast cancer and its clinical significance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547502/ https://www.ncbi.nlm.nih.gov/pubmed/28784153 http://dx.doi.org/10.1186/s13058-017-0884-8 |
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