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Author Spotlight: Unlocking Insights into the Immune Cell Landscape of Tumors
Published on: August 18, 2023
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Genomic Characteristics Related to Histology-Based Immune Features in Breast Cancer
Yoon Jin Cha1, Constandina E O'Connell2, Benjamin C Calhoun2
1Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Summary
Breast cancer subtypes have distinct immune microenvironments. Intratumor immune cells like tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLS) correlate with better patient survival, especially in HER2-enriched and basal-like tumors.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- The tumor microenvironment, particularly immune cells like tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLS), significantly influences breast cancer progression.
- These immune components are increasingly recognized for their clinical relevance in breast cancer patients.
Purpose of the Study:
- To evaluate immune-related histology features in breast cancer using whole-slide images.
- To analyze the association of these features with gene expression, PAM50 subtypes, and patient survival.
- To identify distinct immune microenvironments across different breast cancer subtypes.
Main Methods:
- Whole-slide hematoxylin and eosin (H&E) images from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset were analyzed for TILs, plasma cells (PCs), high-endothelial venule-associated lymphoid aggregates (HALA), and TLS.
- Gene expression signatures for 10 immune features were derived and validated in the Sweden Cancerome Analysis Network - Breast (SCAN-B) cohort.
- Supervised analyses of immune gene expression signatures were performed on high-TIL tumors stratified by PAM50 subtype.
Main Results:
- HER2-enriched (HER2E) and basal-like breast tumors showed higher TILs and PCs.
- HALA and TLS were predominantly found in HER2E and basal-like tumors, with intratumor location associated with better survival.
- Distinct immune microenvironments were identified for each PAM50 subtype, with specific signatures linked to improved survival in high-TIL HER2E (B cells) and basal-like (T cells) tumors.
Conclusions:
- PAM50 subtypes of breast cancer exhibit unique histological and molecular immune microenvironments.
- The location and type of immune infiltrates, particularly intratumor TILs and TLS, are critical prognostic indicators.
- Understanding these subtype-specific immune differences is essential for developing targeted and effective breast cancer treatment strategies.
