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

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.

Download Full-text

Immunomodulating Therapies in Breast Cancer—From Prognosis to Clinical Practice

Cancers ◽

10.3390/cancers13194883 ◽

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.

Download Full-text

Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort.

10.1101/2020.08.19.20177865 ◽

2020 ◽

Author(s):

Pooja Vaid ◽

Anirudha Puntambekar ◽

Rituja Banale ◽

Ruhi Reddy ◽

Rohini Unde ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Prognostic Significance ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Response To Therapy ◽

Stromal Tumor ◽

Breast Cancer Patients ◽

Infiltrating Lymphocytes ◽

Disease Free

Objectives Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC.

Download Full-text