Changes of tumor infiltrating lymphocyte subtypes before and after neoadjuvant endocrine therapy in estrogen receptor-positive breast cancer patients – an immunohistochemical study of cd8+ and foxp3+ using double immunostaining with correlation to the pathobiological response of the patients
Tumor-stromal interactions involve continuous crosstalk and interactions among different cell types and play pivotal roles in tumorigenesis, tumor development, disease progression, subsequent metastasis, and also tumor response to therapeutic agents. Tumor infiltrating lymphocytes (TILs) are importa...
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| creator | Chan, Monica Sm Wang, Lin Felizola, Saulo Ja Ueno, Takayuki Toi, Masakazu Loo, W Chow, Louis Wc Suzuki, Takashi Sasano, Hironobu |
| description | Tumor-stromal interactions involve continuous crosstalk and interactions among different cell types and play pivotal roles in tumorigenesis, tumor development, disease progression, subsequent metastasis, and also tumor response to therapeutic agents. Tumor infiltrating lymphocytes (TILs) are important components of these tumor-stromal interactions. Specific TIL subtypes are known to be involved in the clinical course of individual patients. However, the status of TILs following endocrine therapy has not been studied in breast cancer patients. We evaluated the alterations of TIL subtypes in a cohort of East Asian patients with estrogen receptor-positive breast cancer during the course of neoadjuvant steroidal aromatase inhibitor (AI) therapy, using double immunohistochemical staining of CD8+ and T regulatory cells (Treg) or Foxp3+, yielding the CD8+/Treg ratio in individual patients. Changes in CD8+/Treg ratio before and after therapy were then correlated with pathobiological responses of individual patients based upon alterations of the Ki-67 labeling index (LI). A significant increase in the CD8+/Treg ratio was detected in responders (p=0.028) but not in non-responders, which may reflect the dynamic process in which the host immune response to tumor antigens changed in consequence of an interaction between tumor and stromal cells in its microenvironment following estrogen depletion caused by the AI. The CD8+/Treg ratio in breast cancer tissue can be a potential surrogate marker in surgical pathology specimens for predicting responses to neoadjuvant endocrine therapy, not only incorporating features of carcinoma cells as in Ki-67 LI but also those of adjacent stromal cells in the tumor microenvironment, especially in the early stage of treatment prior to any detectable clinical and/or histopathological changes. |
| doi_str_mv | 10.5301/JBM.2012.10439 |
| format | Article |
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Tumor infiltrating lymphocytes (TILs) are important components of these tumor-stromal interactions. Specific TIL subtypes are known to be involved in the clinical course of individual patients. However, the status of TILs following endocrine therapy has not been studied in breast cancer patients. We evaluated the alterations of TIL subtypes in a cohort of East Asian patients with estrogen receptor-positive breast cancer during the course of neoadjuvant steroidal aromatase inhibitor (AI) therapy, using double immunohistochemical staining of CD8+ and T regulatory cells (Treg) or Foxp3+, yielding the CD8+/Treg ratio in individual patients. Changes in CD8+/Treg ratio before and after therapy were then correlated with pathobiological responses of individual patients based upon alterations of the Ki-67 labeling index (LI). A significant increase in the CD8+/Treg ratio was detected in responders (p=0.028) but not in non-responders, which may reflect the dynamic process in which the host immune response to tumor antigens changed in consequence of an interaction between tumor and stromal cells in its microenvironment following estrogen depletion caused by the AI. The CD8+/Treg ratio in breast cancer tissue can be a potential surrogate marker in surgical pathology specimens for predicting responses to neoadjuvant endocrine therapy, not only incorporating features of carcinoma cells as in Ki-67 LI but also those of adjacent stromal cells in the tumor microenvironment, especially in the early stage of treatment prior to any detectable clinical and/or histopathological changes.</description><identifier>ISSN: 0393-6155</identifier><identifier>EISSN: 1724-6008</identifier><identifier>DOI: 10.5301/JBM.2012.10439</identifier><identifier>PMID: 23280127</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Androstadienes - therapeutic use ; Antineoplastic Agents - therapeutic use ; Aromatase Inhibitors - therapeutic use ; Biomarkers, Tumor - immunology ; Breast Neoplasms - drug therapy ; Breast Neoplasms - immunology ; Breast Neoplasms - pathology ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - pathology ; Clinical Trials as Topic ; Female ; Forkhead Transcription Factors - biosynthesis ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - immunology ; Humans ; Immunohistochemistry ; Lymphocyte Subsets - drug effects ; Lymphocyte Subsets - immunology ; Lymphocyte Subsets - pathology ; Lymphocytes, Tumor-Infiltrating - drug effects ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - pathology ; Neoadjuvant Therapy ; Receptors, Estrogen - biosynthesis ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - pathology</subject><ispartof>The International journal of biological markers, 2012-10, Vol.27 (4), p.295-304</ispartof><rights>2012 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-567f7ed35f5370305568be3566e9dd530f5aa4e429246b4619e57ad36088ae163</citedby><cites>FETCH-LOGICAL-c371t-567f7ed35f5370305568be3566e9dd530f5aa4e429246b4619e57ad36088ae163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.5301/JBM.2012.10439$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.5301/JBM.2012.10439$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21945,27830,27901,27902,44921,45309</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.5301/JBM.2012.10439?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23280127$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chan, Monica Sm</creatorcontrib><creatorcontrib>Wang, Lin</creatorcontrib><creatorcontrib>Felizola, Saulo Ja</creatorcontrib><creatorcontrib>Ueno, Takayuki</creatorcontrib><creatorcontrib>Toi, Masakazu</creatorcontrib><creatorcontrib>Loo, W</creatorcontrib><creatorcontrib>Chow, Louis Wc</creatorcontrib><creatorcontrib>Suzuki, Takashi</creatorcontrib><creatorcontrib>Sasano, Hironobu</creatorcontrib><title>Changes of tumor infiltrating lymphocyte subtypes before and after neoadjuvant endocrine therapy in estrogen receptor-positive breast cancer patients – an immunohistochemical study of cd8+ and foxp3+ using double immunostaining with correlation to the pathobiological response of the patients</title><title>The International journal of biological markers</title><addtitle>Int J Biol Markers</addtitle><description>Tumor-stromal interactions involve continuous crosstalk and interactions among different cell types and play pivotal roles in tumorigenesis, tumor development, disease progression, subsequent metastasis, and also tumor response to therapeutic agents. Tumor infiltrating lymphocytes (TILs) are important components of these tumor-stromal interactions. Specific TIL subtypes are known to be involved in the clinical course of individual patients. However, the status of TILs following endocrine therapy has not been studied in breast cancer patients. We evaluated the alterations of TIL subtypes in a cohort of East Asian patients with estrogen receptor-positive breast cancer during the course of neoadjuvant steroidal aromatase inhibitor (AI) therapy, using double immunohistochemical staining of CD8+ and T regulatory cells (Treg) or Foxp3+, yielding the CD8+/Treg ratio in individual patients. Changes in CD8+/Treg ratio before and after therapy were then correlated with pathobiological responses of individual patients based upon alterations of the Ki-67 labeling index (LI). A significant increase in the CD8+/Treg ratio was detected in responders (p=0.028) but not in non-responders, which may reflect the dynamic process in which the host immune response to tumor antigens changed in consequence of an interaction between tumor and stromal cells in its microenvironment following estrogen depletion caused by the AI. 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Tumor infiltrating lymphocytes (TILs) are important components of these tumor-stromal interactions. Specific TIL subtypes are known to be involved in the clinical course of individual patients. However, the status of TILs following endocrine therapy has not been studied in breast cancer patients. We evaluated the alterations of TIL subtypes in a cohort of East Asian patients with estrogen receptor-positive breast cancer during the course of neoadjuvant steroidal aromatase inhibitor (AI) therapy, using double immunohistochemical staining of CD8+ and T regulatory cells (Treg) or Foxp3+, yielding the CD8+/Treg ratio in individual patients. Changes in CD8+/Treg ratio before and after therapy were then correlated with pathobiological responses of individual patients based upon alterations of the Ki-67 labeling index (LI). A significant increase in the CD8+/Treg ratio was detected in responders (p=0.028) but not in non-responders, which may reflect the dynamic process in which the host immune response to tumor antigens changed in consequence of an interaction between tumor and stromal cells in its microenvironment following estrogen depletion caused by the AI. The CD8+/Treg ratio in breast cancer tissue can be a potential surrogate marker in surgical pathology specimens for predicting responses to neoadjuvant endocrine therapy, not only incorporating features of carcinoma cells as in Ki-67 LI but also those of adjacent stromal cells in the tumor microenvironment, especially in the early stage of treatment prior to any detectable clinical and/or histopathological changes.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>23280127</pmid><doi>10.5301/JBM.2012.10439</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Androstadienes - therapeutic use Antineoplastic Agents - therapeutic use Aromatase Inhibitors - therapeutic use Biomarkers, Tumor - immunology Breast Neoplasms - drug therapy Breast Neoplasms - immunology Breast Neoplasms - pathology CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - pathology Clinical Trials as Topic Female Forkhead Transcription Factors - biosynthesis Forkhead Transcription Factors - genetics Forkhead Transcription Factors - immunology Humans Immunohistochemistry Lymphocyte Subsets - drug effects Lymphocyte Subsets - immunology Lymphocyte Subsets - pathology Lymphocytes, Tumor-Infiltrating - drug effects Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - pathology Neoadjuvant Therapy Receptors, Estrogen - biosynthesis T-Lymphocytes, Regulatory - drug effects T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - pathology |
| title | Changes of tumor infiltrating lymphocyte subtypes before and after neoadjuvant endocrine therapy in estrogen receptor-positive breast cancer patients – an immunohistochemical study of cd8+ and foxp3+ using double immunostaining with correlation to the pathobiological response of the patients |
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