scholarly journals Immune cell composition and immunological profiles of the breast cancer microenvironment represented by histologically assessed tumor-infiltrating lymphocytes and PD-L1 expression: A systematic analysis

2021 ◽  
Author(s):  
Toru Hanamura ◽  
Shigehisa Kitano ◽  
Hiroshi Kagamu ◽  
Makiko Yamashita ◽  
Mayako Terao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Partial Correlation ◽  
Immune Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Leukocyte Infiltration ◽  
Blood Samples ◽  
Tumor Tissues ◽  
Cell Fractions ◽  
Infiltrating Lymphocytes

Abstract Background. A better understanding of tumor immunology can facilitate the development of new treatment strategies for various malignancies. Histologically assessed tumor-infiltrating lymphocytes (hTILs) and programmed cell death 1 ligand 1 (hPD-L1) have been established as prognostic or predictive biomarkers in certain subsets of breast cancer. However, the complexity of multiple types of immune cells is not fully understood. In this study, the immune cell fractions in breast cancer tissue and blood were evaluated to analyze their association with hTILs and hPD-L1. Methods. In total, 45 tumor and 18 blood samples were collected from breast cancer patients. The total leukocyte counts, proportions of 11 types of immune cells in the samples, and PD-L1 expression in each fraction were evaluated using multicolor flow cytometry for both the tumor and blood samples. The hTILs and hPD-L1 were evaluated with hematoxylin and eosin staining and immunohistochemistry respectively. Results. The immune cell composition of the blood showed a partial correlation with that of the tumor tissue; however, no significant association was found between the blood immune cell compositions and hTIL or hPD-L1 expression. A higher hTIL was associated with increased leukocyte infiltration as well as a higher proportion of CD4+ and CD8+ T cells and lower proportion of natural killer cells and natural killer T cells. PD-L1 was highly expressed in the monocyte/macrophage (Mo/Mφ), nonclassical monocyte (CD16+ Mo), myeloid-derived suppressor cell (MDSC), dendritic cell (DC), and myeloid dendritic cell (mDC) fractions in the tumor tissues. hPD-L1 positivity was associated with increased leukocyte infiltration in the tumor tissues and PD-L1 expression in Mo/Mφ, CD16+ Mo, MDSC, DC, and mDC fractions. Conclusion. There was a partial correlation in the composition of immune cells at the tumor site and that in the peripheral blood. A high proportion of hTILs reflects not only higher immune cell infiltration but also differences in the immune responses in the tumor microenvironment. Non-B-cell antigen-presenting cell fractions such as Mo/Mφ, CD16+ Mo, MDSC, DC, and mDC fractions are involved primarily in the PD-L1 pathway in the breast cancer microenvironments.

scholarly journals Immunological Profiles of The Breast Cancer Microenvironment Represented by Tumor-Infiltrating Lymphocytes and PD-L1 Expression

2021 ◽  
Author(s):  
Toru Hanamura ◽  
Shigehisa Kitano ◽  
Hiroshi Kagamu ◽  
Makiko Yamashita ◽  
Mayako Terao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
B Cell ◽  
Natural Killer ◽  
Immune Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Leukocyte Infiltration ◽  
Cell Fractions ◽  
Antigen Presenting ◽  
Infiltrating Lymphocytes

Abstract Purpose: Histologically assessed tumor-infiltrating lymphocytes and programmed cell death 1 ligand 1 (hPD-L1) are established prognostic or predictive biomarkers in certain subsets of breast cancer. However, the association with immune response complexity is not fully understood. In this study, the immune cell fractions in breast cancer tissue and blood were evaluated to analyze their association with histologically assessed tumor-infiltrating lymphocytes and PD-L1. Methods: Forty-five tumor and 18 blood samples were collected from patients with breast cancer. Total leukocyte counts, proportions of 11 types of immune cells, and PD-L1 expression in each cell fraction were evaluated using multicolor flow cytometry. Histologically assessed tumor-infiltrating lymphocytes and PD-L1 were evaluated using hematoxylin and eosin staining and immunohistochemistry, respectively. Results: The immune cell composition of blood was partly correlated with that of tumor tissue but the abundance ratio of each fraction was different between them. A higher histologically assessed tumor-infiltrating lymphocyte proportion was associated with increased leukocyte infiltration, a higher proportion of CD4+ and CD8+ T cells, and a lower proportion of natural killer cells and natural killer T cells. PD-L1 was highly expressed in the non-B-cell antigen-presenting cell fractions (monocyte/macrophage, nonclassical monocyte, myeloid-derived suppressor, dendritic, and myeloid dendritic cell) in tumors. Histologically assessed PD-L1 positivity reflected PD-L1 expression well in these fractions, as well as increased leukocyte infiltration in tumors. Conclusion: Our results indicate that histologically assessed tumor-infiltrating lymphocytes reflect differences in immune responses in the tumor microenvironment. Non-B-cell antigen-presenting cell fractions are primarily involved in the PD-L1 pathway in breast cancer microenvironments.

scholarly journals Immunomodulating Therapies in Breast Cancer—From Prognosis to Clinical Practice

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4883
Author(s):  
Marcus Schmidt ◽  
Anne-Sophie Heimes
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Chemotherapy ◽  
Infiltrating Lymphocytes

The role of the immune system in breast cancer has been debated for decades. The advent of technologies such as next generation sequencing (NGS) has elucidated the crucial interplay between somatic mutations in tumors leading to neoantigens and immune responses with increased tumor-infiltrating lymphocytes and improved prognosis of breast cancer patients. In particular, triple-negative breast cancer (TNBC) has a higher mutational burden compared to other breast cancer subtypes. In addition, higher levels of tumor-associated antigens suggest that immunotherapies are a promising treatment option, specifically for TNBC. Indeed, higher concentrations of tumor-infiltrating lymphocytes are associated with better prognosis and response to chemotherapy in TNBC. An important target within the cancer immune cell cycle is the “immune checkpoint”. Immune checkpoint inhibitors (ICPis) block the interaction of certain cell surface proteins that act as “brakes” on immune responses. Recent studies have shown that ICPis improve survival in both early and advanced TNBC. However, this comes at the price of increased toxicity, particularly immune-mediated toxicity. As an alternative approach, individualized mRNA vaccination strategies against tumor-associated neoantigens represent another promising approach leading to neoantigen-specific immune responses. These novel strategies should help to improve treatment outcomes, especially for patients with triple negative breast cancer.

scholarly journals The Leptin Axis and Its Association With the Adaptive Immune System in Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura García-Estevez ◽  
Silvia González-Martínez ◽  
Gema Moreno-Bueno
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Immune System ◽  
Immune Cells ◽  
Leptin Receptor ◽  
Adaptive Immune System ◽  
Tumor Infiltrating Lymphocytes ◽  
Cancer Subtypes ◽  
Adaptive Immune ◽  
Infiltrating Lymphocytes

Adipose tissue secretes various peptides, including leptin. This hormone acts through the leptin receptor (Ob-R), which is expressed ubiquitously on the surface of various cells, including breast cancer cells and immune cells. Increasing evidence points to an interaction between the tumor microenvironment, tumor cells, and the immune system. Leptin plays an important role in breast cancer tumorigenesis and may be implicated in activation of the immune system. While breast cancer cannot be considered an immunogenic cancer, the triple-negative subtype is an exception. Specific immune cells - tumor infiltrating lymphocytes - are involved in the immune response and act as predictive and prognostic factors in certain breast cancer subtypes. The aim of this article is to review the interaction between adipose tissue, through the expression of leptin and its receptor, and the adaptive immune system in breast cancer.

scholarly journals Racial/Ethnic Differences Among Tumor Infiltrating Lymphocytes in Breast Cancer Tumors

2021 ◽  
Author(s):  
Surbhi Bansil ◽  
Anthony Silva ◽  
Alana Taniguchi ◽  
Christina Wiedmer ◽  
Mayumi Fernandez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Ethnic Groups ◽  
Ethnic Differences ◽  
Immune Cell ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes ◽  
Racial Ethnic

Abstract PurposeTumor infiltrating lymphocytes (TILs) have emerged as a predictor of cancer treatment response and patient outcomes, including for breast cancer. Current studies investigating racial/ethnic differences in TILs and immune profiles in breast cancer offer varying results. Our study hopes to address the paucity of data in breast cancer tumor microenvironment from different racial/ethnic groups not well represented in the literature.MethodsWe reviewed 183 cases of women diagnosed with early stage breast cancer who received neoadjuvant treatment at two large health systems in Hawaii between 2008 and 2020. We evaluated clinical and demographic information including: age at diagnosis, race/ethnicity, tumor stage, tumor subtype according to ER, PR, and HER2 receptor status and compared them with obtaining a pathologic complete response (pCR) and amount of stromal TILs (sTILs).ResultsWe found a significantly greater amount of sTILs in Asians (37.7%, p=0.01) and Native Hawaiian/Pacific Islander (NHPI) (37.2%, p=0.02) patients compared to White patients on multivariate analysis. We found no significant differences in pCR among the different racial/ethnic groups.ConclusionsRacial/ethnic differences in the amount of sTILs in breast cancer tumors suggest that higher sTIL percentages alone do not predict for pCR. Increases in sTILs in Asian and NHPI patients suggest differences in immune cell profiles in the breast tumor microenvironment. This may in part contribute to known outcome disparities in these populations.

scholarly journals A Study on Tumor-Infiltrating Lymphocytes in Different Subtypes of Breast Cancer

2021 ◽  
Vol 14 (1) ◽  
pp. 70-81
Author(s):  
Polina D. Dimitrova ◽  
Savelina L. Popovska ◽  
Ivan N. Ivanov
Keyword(s):  
Breast Cancer ◽  
T Regulatory Cells ◽  
Immune Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Treg Cells ◽  
Luminal A ◽  
Her2 Positive ◽  
High Count ◽  
Luminal B ◽  
Infiltrating Lymphocytes

Summary The study aimed to investigate immune cell infiltration in different subtypes of breast cancer (BC). Retrospectively were selected 100 patients with primary BC, grouped into four molecular surrogate subtypes (Luminal A and Luminal B-like, HER2-positive and triple-negative - TN), determined by immunohistochemistry (IHC). In each patient, a percentage of stromal tumor-infiltrating lymphocytes (TILs) was determined by hematoxylin-eosin staining. IHC was performed using primary antibodies CD3, CD4, CD8, CD20, and FOXP3. Immunophenotyped lymphocytes were counted (separately intratumoral and stromal) and semi-quantitatively graded. In the studied tumors, 10% were defined as lymphocyte-predominant BC. A high count of intratumoral and stromal TILs subsets was found mainly in TN and HER2-positive BC. The stroma is the preferred localization for immune cells in all four BC subtypes. CD3+ T predominates over CD20+ B lymphocytes, with CD8+ T cytotoxic and FoxP3+ T regulatory cells dominating T subtypes. HER2 and TN are more immunogenic than Luminal A and Luminal B – like subtypes of BC. The T-cells’ immune response was predominant in the studied cases of BC, with a predominance of CD8+ Tc and Foxp3+ Treg cells located mainly in the stroma.

scholarly journals ITGA3 Is Associated With Immune Cell Infiltration and Serves as a Favorable Prognostic Biomarker for Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yue Li ◽  
Fan Li ◽  
Xiaoyu Bai ◽  
Yanlei Li ◽  
Chunsheng Ni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Immune Cells ◽  
Immune Cell ◽  
Genomic Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Diagnostic Value ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Breast Cancer Patients

BackgroundITGA3 is a member of the integrin family, a cell surface adhesion molecule that can interact with extracellular matrix (ECM) proteins. The purpose of this study was to explore the significance of ITGA3 expression in the prognosis and clinical diagnosis of breast cancer patients.MethodsOncomine, the Human Protein Atlas (HPA) and UALCAN were used to analyze the expression of ITGA3 in various cancers. PrognoScan, GEPIA, Kaplan–Meier plotter and Easysurv were utilized to analyze the prognosis of ITGA3 in certain cancers. Based on TCGA data, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of ITGA3 expression. cBio-Portal and MethSurv were used to evaluate the genomic mechanism. LinkedOmics, NetworkAnalyst and Metascape were used to build the signaling network. TIMER is a web server for comprehensive analysis of tumor infiltrating immune cells and tumor infiltrating lymphocytes (TILs).ResultsThe expression of ITGA3 in normal breast tissues was greater than that in breast cancer tissues at both the mRNA and protein levels. High expression of ITGA3 was associated with better prognosis of breast cancer patients. ROC analysis indicated that ITGA3 had significant diagnostic value. Genomic analysis revealed that promoter methylation of ITGA3 leads to transcriptional silencing, which may be one of the mechanisms underlying ITGA3 downregulation in BRCA. Immune infiltration analysis showed that ITGA3 may be involved in the recruitment of immune cells.ConclusionsThis study identified ITGA3 as a novel biomarker to estimate the diagnosis and prognosis of breast cancer. In addition, ITGA3 is involved in ECM regulation and immune cell infiltration.

Clinical significance and immunogenomic landscape analyses of the immune cell signature based prognostic model for patients with breast cancer

2020 ◽  
Author(s):  
Shiyuan Wang ◽  
Yuqiang Xiong ◽  
Qi Zhang ◽  
Dongqing Su ◽  
Chunlu Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Risk Score ◽  
Prognostic Model ◽  
Immune Cell ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Cancer Patients ◽  
Therapeutic Benefits ◽  
Response To Chemotherapy ◽  
Infiltrating Lymphocytes

Abstract Breast cancer is one of the most common types of cancers and the leading cause of death from malignancy among women worldwide. Tumor-infiltrating lymphocytes are a source of important prognostic biomarkers for breast cancer patients. In this study, based on the tumor-infiltrating lymphocytes in the tumor immune microenvironment, a risk score prognostic model was developed in the training cohort for risk stratification and prognosis prediction in breast cancer patients. The prognostic value of this risk score prognostic model was also verified in the two testing cohorts and the TCGA pan cancer cohort. Nomograms were also established in the training and testing cohorts to validate the clinical use of this model. Relationships between the risk score, intrinsic molecular subtypes, immune checkpoints, tumor-infiltrating immune cell abundances and the response to chemotherapy and immunotherapy were also evaluated. Based on these results, we can conclude that this risk score model could serve as a robust prognostic biomarker, provide therapeutic benefits for the development of novel chemotherapy and immunotherapy, and may be helpful for clinical decision making in breast cancer patients.

scholarly journals Crosstalk between Tumor-Infiltrating Immune Cells and Cancer-Associated Fibroblasts in Tumor Growth and Immunosuppression of Breast Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jarupa Soongsathitanon ◽  
Pranisa Jamjuntra ◽  
Nuttavut Sumransub ◽  
Supaporn Yangngam ◽  
Marjorie De la Fuente ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Cancer Associated Fibroblasts ◽  
Stromal Component ◽  
The Impact

Signals from the tumor microenvironment (TME) have a profound influence on the maintenance and progression of cancers. Chronic inflammation and the infiltration of immune cells in breast cancer (BC) have been strongly associated with early carcinogenic events and a switch to a more immunosuppressive response. Cancer-associated fibroblasts (CAFs) are the most abundant stromal component and can modulate tumor progression according to their secretomes. The immune cells including tumor-infiltrating lymphocytes (TILs) (cytotoxic T cells (CTLs), regulatory T cells (Tregs), and helper T cell (Th)), monocyte-infiltrating cells (MICs), myeloid-derived suppressor cells (MDSCs), mast cells (MCs), and natural killer cells (NKs) play an important part in the immunological balance, fluctuating TME between protumoral and antitumoral responses. In this review article, we have summarized the impact of these immunological players together with CAF secreted substances in driving BC progression. We explain the crosstalk of CAFs and tumor-infiltrating immune cells suppressing antitumor response in BC, proposing these cellular entities as predictive markers of poor prognosis. CAF-tumor-infiltrating immune cell interaction is suggested as an alternative therapeutic strategy to regulate the immunosuppressive microenvironment in BC.

Sign in / Sign up

Export Citation Format

Share Document