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 Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes

2021 ◽  
Author(s):  
H. Kuroda ◽  
T. Jamiyan ◽  
R. Yamaguchi ◽  
A. Kakumoto ◽  
A. Abe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Associated Macrophages ◽  
Free Survival ◽  
Infiltrating Lymphocytes

Abstract Purpose Immune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated. Methods We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. Results TNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. Conclusions Our study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings.

scholarly journals Impact of the Tumor Microenvironment on Tumor-Infiltrating Lymphocytes: Focus on Breast Cancer

2017 ◽  
Vol 11 ◽  
pp. 117822341773156 ◽  
Author(s):  
Ivan J Cohen ◽  
Ronald Blasberg
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Clinical Trials ◽  
Tumor Microenvironment ◽  
Immune Checkpoint ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Tumors ◽  
Immune Checkpoint Blockade ◽  
Physical Barriers ◽  
Infiltrating Lymphocytes

Immunotherapy is revolutionizing cancer care across disciplines. The original success of immune checkpoint blockade in melanoma has already been translated to Food and Drug Administration–approved therapies in a number of other cancers, and a large number of clinical trials are underway in many other disease types, including breast cancer. Here, we review the basic requirements for a successful antitumor immune response, with a focus on the metabolic and physical barriers encountered by lymphocytes entering breast tumors. We also review recent clinical trials of immunotherapy in breast cancer and provide a number of interesting questions that will need to be answered for successful breast cancer immunotherapy.

Impact of dual anti-HER2 therapy on pathologic complete response rate in breast cancer in a minority-enriched population.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18111-e18111 ◽  
Author(s):  
Jenny Jing Li ◽  
Hsiao Ching Li ◽  
Ang Gao ◽  
Samira K. Syed ◽  
Nisha Unni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Complete Response Rate ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Safety Net ◽  
Her2 Breast Cancer ◽  
Race Ethnicity ◽  
Pathologic Complete Response Rate ◽  
Racial Ethnic

e18111 Background: The addition of pertuzumab (P) to a neoadjuvant trastuzumab (H) plus chemotherapy combination has been shown to significantly improve the pathologic complete response rate (pCR) in localized HER2+ breast cancer; however, minorities have been under-represented in these trials. Racial/ethnic disparities have also been shown to affect outcomes of cancer treatment. This study is aimed to assess the impact of neoadjuvant dual HER2-blockade in an unselected minority-enriched population. Methods: A retrospective chart review was conducted of women with stage I to III HER2+ breast cancer who received neoadjuvant treatment between 2007 and 2017 at an academic institution and its affiliated safety net health system. Data on stage, chemotherapy, race/ethnicity, site of therapy (academic vs safety net hospital), and hormone receptor status were collected. All patients underwent surgery after completion of neoadjuvant chemotherapy. pCR was defined as ypT0/is, ypN0. Chi-squared test and univariate/multivariate logistic regression were used for statistical analysis. Results: The study population included 261 women with the following race/ethnic distribution: 37.7% Non-Hispanic Whites, 34.6% Hispanics, 20.6% Blacks, and 7% other racial/ethnic origin. Ninety-five patients (36%) received chemotherapy-H vs 166 patients (64%) received chemotherapy-HP. Patients at the safety net health system had higher stage at diagnosis compared to the academic site. Site of care and race/ethnicity did not impact the choice of neoadjuvant treatment. The pCR rate was significantly higher for the chemotherapy-HP group (55.4%) compared to the chemotherapy-H group (34.7%) (p = 0.001). There was no association between race/ethnicity, or site of treatment (academic vs safety net), and the probability of achieving pCR. Multivariate analysis showed only dual anti-HER2 therapy (OR: 2.67, CI: 1.55-4.59, p = 0.0004) and hormone-receptor negative status (OR: 2.18, CI: 1.30-3.67, p = 0.0031) to correlate with pCR. Conclusions: Neoadjuvant dual anti-HER2 therapy was more likely to result in a pCR in our minority enriched population. Our data also suggests the combination of chemotherapy-HP confers similar benefit irrespective of race/ethnicity or site of care.

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 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 Tumor Microenvironment in Breast Cancer—Updates on Therapeutic Implications and Pathologic Assessment

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4233
Author(s):  
Joshua J. Li ◽  
Julia Y. Tsang ◽  
Gary M. Tse
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Treatment Decision ◽  
Tumor Infiltrating Lymphocytes ◽  
Therapeutic Implications ◽  
Cancer Management ◽  
Breast Cancer Management ◽  
Pathologic Assessment ◽  
Infiltrating Lymphocytes

The tumor microenvironment (TME) in breast cancer comprises local factors, cancer cells, immune cells and stromal cells of the local and distant tissues. The interaction between cancer cells and their microenvironment plays important roles in tumor proliferation, propagation and response to therapies. There is increasing research in exploring and manipulating the non-cancerous components of the TME for breast cancer treatment. As the TME is now increasingly recognized as a treatment target, its pathologic assessment has become a critical component of breast cancer management. The latest WHO classification of tumors of the breast listed stromal response pattern/fibrotic focus as a prognostic factor and includes recommendations on the assessment of tumor infiltrating lymphocytes and PD-1/PD-L1 expression, with therapeutic implications. This review dissects the TME of breast cancer, describes pathologic assessment relevant for prognostication and treatment decision, and details therapeutic options that interacts with and/or exploits the TME in breast cancer.

Tumor infiltrating lymphocytes and programmed death ligand-1 can identify different prognostic profiles in breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12622-e12622
Author(s):  
Omar Peña-Curiel ◽  
Alejandro Aranda-Gutierrez ◽  
Gabriela S. Gómez-Macías ◽  
Carlos Herrera-López ◽  
Ana Sofia Ferrigno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Model ◽  
Pathologic Complete Response ◽  
Tumor Infiltrating Lymphocytes ◽  
Ongoing Research ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Infiltrating Lymphocytes

e12622 Background: Immunologic biomarkers such as tumor infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) can provide prognostic information in breast cancer (BC) patients. Specifically, a high TILs level has been associated with pathologic complete response and enhanced disease-free survival (DFS). Furthermore, PD-L1 positivity has been associated with worse DFS and overall survival (OS). However, the interaction of both biomarkers as well as its association with survival outcomes in specific BC subtypes is still a subject of ongoing research. Methods: Medical records of women diagnosed with primary BC between 2013 and 2015 in a center in Monterrey, Mexico were reviewed. Eligible patients had at least 1 year of follow-up, stages I-III at diagnosis, and available tissue for TILs and PD-L1 assessment. PD-L1 positivity was defined as the presence of PD-L1 in ≥1% of tumor-infiltrating immune cells using the VENTANA SP142 assay. Classification of TILs into low ( < 30%) and high (≥30%) levels was performed for analytical purposes. Clinicopathological features were compared with Fisher’s exact tests and logistic regression models, as appropriate. The Kaplan-Meier method was used to calculate recurrence-free survival (RFS), and associations between variables were explored with log-rank or Cox regressions. Results: A total of 195 patients were included. Overall, 12.3% of BC biopsy specimens showed positivity to PD-L1 (8.3% [11/132] in HR+/HER2-, 5.9% [2/34] in HER2+, and 38% [11/29] in TNBC; p < 0.001). PD-L1 positivity was significantly associated with ER-negative status (OR 3.1; p = 0.013), high TILs (OR 5.7; p < 0.001), and high Ki67 expression (HR 12.5; p < 0.001). The median follow-up for the entire cohort was 61 months (95%CI 58-63). RFS in the PD-L1- group was significantly superior to the PD-L1+ group (85% vs. 66% at 5 years; p = 0.021). In a multivariate Cox model, PD-L1 positivity (HR 3.3), low TILs (HR 3.4), advanced stage (HR 2.8), and high histological grade (HR 2.5) were all independent prognostic factors for worse RFS. Based on these results, we further classified our cohort into four prognostic profiles based on PD-L1 and TILs status. The low TILs/PD-L1+ group experienced an inferior RFS than low TILs/PD-L1- patients (45% vs. 85% at 5-years; p-value < 0.001), while no difference was observed in the high TILs groups. Notably, when analyzing HR+/HER2- patients only, a similar statistical difference was observed between low TILs/PD-L1+ and low TILs/PD-L1- groups (HR 5.4, p = 0.009). Conclusions: In our cohort, PD-L1 positivity together with low TILs identified a subset of BC patients with a worse RFS. Interestingly, patients with HR+/HER2- BC fared worse in the low TILs/PD-L1+ subcategory than in the low TILs/PD-L1- group. Future studies are warranted to explore the prognostic value of categorizing patients based on TILs and PD-L1 status in different BC subtypes.

Abstract P6-06-13: Racial/ethnic differences in tumor infiltrating lymphocytes

2020 ◽  
Author(s):  
Jami Fukui ◽  
Alana Taniguchi ◽  
Madison Meister ◽  
Ian Pagano ◽  
Jeffrey Killeen
Keyword(s):  
Ethnic Differences ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes ◽  
Racial Ethnic
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