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Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy

BACKGROUND: Tumour-infiltrating lymphocyte (TIL)-high breast tumours have a high rate of pathological complete response (pCR) with neoadjuvant chemotherapy. In our routine pathological diagnoses of biopsy specimens from pCR cases, we have observed a high infiltration of plasma cells (PCs). A positiv...

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Autores principales: Sakaguchi, Asumi, Horimoto, Yoshiya, Onagi, Hiroko, Ikarashi, Daiki, Nakayama, Takayuki, Nakatsura, Tetsuya, Shimizu, Hideo, Kojima, Kuniaki, Yao, Takashi, Matsumoto, Toshiharu, Ogura, Kanako, Kitano, Shigehisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555250/
https://www.ncbi.nlm.nih.gov/pubmed/34715905
http://dx.doi.org/10.1186/s13058-021-01477-w
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author Sakaguchi, Asumi
Horimoto, Yoshiya
Onagi, Hiroko
Ikarashi, Daiki
Nakayama, Takayuki
Nakatsura, Tetsuya
Shimizu, Hideo
Kojima, Kuniaki
Yao, Takashi
Matsumoto, Toshiharu
Ogura, Kanako
Kitano, Shigehisa
author_facet Sakaguchi, Asumi
Horimoto, Yoshiya
Onagi, Hiroko
Ikarashi, Daiki
Nakayama, Takayuki
Nakatsura, Tetsuya
Shimizu, Hideo
Kojima, Kuniaki
Yao, Takashi
Matsumoto, Toshiharu
Ogura, Kanako
Kitano, Shigehisa
author_sort Sakaguchi, Asumi
collection PubMed
description BACKGROUND: Tumour-infiltrating lymphocyte (TIL)-high breast tumours have a high rate of pathological complete response (pCR) with neoadjuvant chemotherapy. In our routine pathological diagnoses of biopsy specimens from pCR cases, we have observed a high infiltration of plasma cells (PCs). A positive correlation of PCs with favourable patient outcome has recently been reported, but little is known about how PCs contribute to local tumour immunity. METHODS: We retrospectively examined biopsy specimens from 146 patients with invasive breast cancer who received neoadjuvant chemotherapy. CD138(+) PC infiltration was assessed by immunohistochemistry. Multiplexed fluorescent immunohistochemistry (mfIHC) with T and B cell markers was also conducted to elucidate the profile of immune cells. RESULTS: Greater PC infiltration was observed in the pCR group (p = 0.028) and this trend was confirmed in another patient cohort. With mfIHC, we observed significantly more CD8(+), T-bet(+)CD4(+), and CD8(+)FOXP3(+) T cells, total B cells and PCs in pCR cases. Such cases were also characterised by high expression of both PD-1 and PD-L1 on B cells and PCs. In patients with hormone receptor-negative tumours, high PC infiltration was correlated with significantly longer disease-free survival (p = 0.034). CONCLUSIONS: We found that higher PC infiltration in biopsy specimens before neoadjuvant chemotherapy was associated with pCR. With mfIHC, we also revealed that the local cytotoxic immune response was clearly enhanced in pCR cases, as was the infiltration of B cells including PCs. Moreover, higher PC levels were correlated with favourable outcomes in hormone receptor-negative breast cancer patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-021-01477-w.
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spelling pubmed-85552502021-10-29 Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy Sakaguchi, Asumi Horimoto, Yoshiya Onagi, Hiroko Ikarashi, Daiki Nakayama, Takayuki Nakatsura, Tetsuya Shimizu, Hideo Kojima, Kuniaki Yao, Takashi Matsumoto, Toshiharu Ogura, Kanako Kitano, Shigehisa Breast Cancer Res Research Article BACKGROUND: Tumour-infiltrating lymphocyte (TIL)-high breast tumours have a high rate of pathological complete response (pCR) with neoadjuvant chemotherapy. In our routine pathological diagnoses of biopsy specimens from pCR cases, we have observed a high infiltration of plasma cells (PCs). A positive correlation of PCs with favourable patient outcome has recently been reported, but little is known about how PCs contribute to local tumour immunity. METHODS: We retrospectively examined biopsy specimens from 146 patients with invasive breast cancer who received neoadjuvant chemotherapy. CD138(+) PC infiltration was assessed by immunohistochemistry. Multiplexed fluorescent immunohistochemistry (mfIHC) with T and B cell markers was also conducted to elucidate the profile of immune cells. RESULTS: Greater PC infiltration was observed in the pCR group (p = 0.028) and this trend was confirmed in another patient cohort. With mfIHC, we observed significantly more CD8(+), T-bet(+)CD4(+), and CD8(+)FOXP3(+) T cells, total B cells and PCs in pCR cases. Such cases were also characterised by high expression of both PD-1 and PD-L1 on B cells and PCs. In patients with hormone receptor-negative tumours, high PC infiltration was correlated with significantly longer disease-free survival (p = 0.034). CONCLUSIONS: We found that higher PC infiltration in biopsy specimens before neoadjuvant chemotherapy was associated with pCR. With mfIHC, we also revealed that the local cytotoxic immune response was clearly enhanced in pCR cases, as was the infiltration of B cells including PCs. Moreover, higher PC levels were correlated with favourable outcomes in hormone receptor-negative breast cancer patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-021-01477-w. BioMed Central 2021-10-29 2021 /pmc/articles/PMC8555250/ /pubmed/34715905 http://dx.doi.org/10.1186/s13058-021-01477-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Sakaguchi, Asumi
Horimoto, Yoshiya
Onagi, Hiroko
Ikarashi, Daiki
Nakayama, Takayuki
Nakatsura, Tetsuya
Shimizu, Hideo
Kojima, Kuniaki
Yao, Takashi
Matsumoto, Toshiharu
Ogura, Kanako
Kitano, Shigehisa
Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy
title Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy
title_full Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy
title_fullStr Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy
title_full_unstemmed Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy
title_short Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy
title_sort plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555250/
https://www.ncbi.nlm.nih.gov/pubmed/34715905
http://dx.doi.org/10.1186/s13058-021-01477-w
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