Immunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expression
Abstract Tumor-infiltrating lymphocytes (TILs) and programmed cell death 1 ligand 1 (PD-L1) are established prognostic and predictive biomarkers for certain breast cancer subsets. However, their association with the immune response complexity is not fully understood. Therefore, we analyzed the assoc...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-11578-x |
| _version_ | 1818238994666749952 |
|---|---|
| author | Toru Hanamura Shigehisa Kitano Hiroshi Kagamu Makiko Yamashita Mayako Terao Banri Tsuda Takuho Okamura Nobue Kumaki Katsuto Hozumi Naoki Harada Takayuki Iwamoto Chikako Honda Sasagu Kurozumi Naoki Niikura |
| author_facet | Toru Hanamura Shigehisa Kitano Hiroshi Kagamu Makiko Yamashita Mayako Terao Banri Tsuda Takuho Okamura Nobue Kumaki Katsuto Hozumi Naoki Harada Takayuki Iwamoto Chikako Honda Sasagu Kurozumi Naoki Niikura |
| author_sort | Toru Hanamura |
| collection | DOAJ |
| description | Abstract Tumor-infiltrating lymphocytes (TILs) and programmed cell death 1 ligand 1 (PD-L1) are established prognostic and predictive biomarkers for certain breast cancer subsets. However, their association with the immune response complexity is not fully understood. Therefore, we analyzed the association between the immune cell fractions in breast cancer tissues and histologically assessed TIL (hTIL) and PD-L1 (hPD-L1). Forty-five tumor and eighteen blood samples were collected from patients with breast cancer. Total leukocyte counts, frequency of 11 immune cell populations, and PD-L1 expression in each cell fraction were evaluated by flow cytometry. TILs and PD-L1 were assessed by hematoxylin and eosin staining and immunohistochemistry, respectively. A higher hTIL score showed association with increased leukocyte infiltration, higher CD4+ and CD8+ T cell proportions, and lower natural killer and natural killer T cell proportions. PD-L1 was highly expressed in nonclassical monocytes, monocyte/macrophages, myeloid-derived suppressor cells, myeloid dendritic cells, dendritic cells, and other lineages in tumors. hPD-L1 positivity reflected PD-L1 expression accurately in these fractions, as well as increased leukocyte infiltration in tumors. These results indicate that hTILs reflect differences in the immune responses in the tumor microenvironment, and certain immune cell fractions are favorably expressed in the PD-L1 pathway in breast cancer microenvironments. |
| first_indexed | 2024-12-12T12:50:30Z |
| format | Article |
| id | doaj.art-5b61e7baafcc4346bcc32f7c5197e00c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T12:50:30Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5b61e7baafcc4346bcc32f7c5197e00c2022-12-22T00:24:00ZengNature PortfolioScientific Reports2045-23222022-05-0112111010.1038/s41598-022-11578-xImmunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expressionToru Hanamura0Shigehisa Kitano1Hiroshi Kagamu2Makiko Yamashita3Mayako Terao4Banri Tsuda5Takuho Okamura6Nobue Kumaki7Katsuto Hozumi8Naoki Harada9Takayuki Iwamoto10Chikako Honda11Sasagu Kurozumi12Naoki Niikura13Department of Breast Oncology, Tokai University School of MedicineDivision of Cancer Immunotherapy Development, Center for Advanced Medical Development, The Cancer Institute Hospital of JFCRDivision of Respiratory Medicine, Saitama Medical University International Medical CenterDivision of Cancer Immunotherapy Development, Center for Advanced Medical Development, The Cancer Institute Hospital of JFCRDepartment of Breast Oncology, Tokai University School of MedicineDepartment of Breast Oncology, Tokai University School of MedicineDepartment of Breast Oncology, Tokai University School of MedicineDepartment of Pathology, Tokai University School of MedicineDepartment of Immunology, Tokai University School of MedicineProduct Research Department, Chugai Pharmaceutical Co., Ltd.Breast and Endocrine Surgery, Okayama University HospitalDepartment of General Surgical Science, Gunma University Graduate School of MedicineDepartment of Breast Surgery, International University of Health and WelfareDepartment of Breast Oncology, Tokai University School of MedicineAbstract Tumor-infiltrating lymphocytes (TILs) and programmed cell death 1 ligand 1 (PD-L1) are established prognostic and predictive biomarkers for certain breast cancer subsets. However, their association with the immune response complexity is not fully understood. Therefore, we analyzed the association between the immune cell fractions in breast cancer tissues and histologically assessed TIL (hTIL) and PD-L1 (hPD-L1). Forty-five tumor and eighteen blood samples were collected from patients with breast cancer. Total leukocyte counts, frequency of 11 immune cell populations, and PD-L1 expression in each cell fraction were evaluated by flow cytometry. TILs and PD-L1 were assessed by hematoxylin and eosin staining and immunohistochemistry, respectively. A higher hTIL score showed association with increased leukocyte infiltration, higher CD4+ and CD8+ T cell proportions, and lower natural killer and natural killer T cell proportions. PD-L1 was highly expressed in nonclassical monocytes, monocyte/macrophages, myeloid-derived suppressor cells, myeloid dendritic cells, dendritic cells, and other lineages in tumors. hPD-L1 positivity reflected PD-L1 expression accurately in these fractions, as well as increased leukocyte infiltration in tumors. These results indicate that hTILs reflect differences in the immune responses in the tumor microenvironment, and certain immune cell fractions are favorably expressed in the PD-L1 pathway in breast cancer microenvironments.https://doi.org/10.1038/s41598-022-11578-x |
| spellingShingle | Toru Hanamura Shigehisa Kitano Hiroshi Kagamu Makiko Yamashita Mayako Terao Banri Tsuda Takuho Okamura Nobue Kumaki Katsuto Hozumi Naoki Harada Takayuki Iwamoto Chikako Honda Sasagu Kurozumi Naoki Niikura Immunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expression Scientific Reports |
| title | Immunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expression |
| title_full | Immunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expression |
| title_fullStr | Immunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expression |
| title_full_unstemmed | Immunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expression |
| title_short | Immunological profiles of the breast cancer microenvironment represented by tumor-infiltrating lymphocytes and PD-L1 expression |
| title_sort | immunological profiles of the breast cancer microenvironment represented by tumor infiltrating lymphocytes and pd l1 expression |
| url | https://doi.org/10.1038/s41598-022-11578-x |
| work_keys_str_mv | AT toruhanamura immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT shigehisakitano immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT hiroshikagamu immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT makikoyamashita immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT mayakoterao immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT banritsuda immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT takuhookamura immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT nobuekumaki immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT katsutohozumi immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT naokiharada immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT takayukiiwamoto immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT chikakohonda immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT sasagukurozumi immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression AT naokiniikura immunologicalprofilesofthebreastcancermicroenvironmentrepresentedbytumorinfiltratinglymphocytesandpdl1expression |