Tumor-Infiltrating Lymphocytes (TILs) in Early Breast Cancer Patients: High CD3+, CD8+, and Immunoscore Are Associated with a Pathological Complete Response
Open accessAbstract
Background: Tumor-infiltrating lymphocytes are associated with a better prognosis in early triple-negative breast cancer (TNBC). These cells can be enumerated in situ by the “Immunoscore Clinical Research” (ISCR). The original Immunoscore® is a prognostic tool that categorizes the densities of CD3+ and CD8+ cells in both the invasive margin (IM) and center of the tumor (CT) in localized colon cancer, yielding a five-tiered classification (0–4). We evaluated the prognostic potential of ISCR and pathological complete response (pCR) following neoadjuvant chemotherapy (NACT). Methods: The cohort included 53 TNBC, 32 luminal BC, and 18 HER2-positive BC patients undergoing NACT. Pre-treatment tumor biopsies were immune-stained for CD3+ and CD8+ T-cell markers. Quantitative analysis of these cells in different tumor locations was performed using computer-assisted image analysis. Results: The pCR rate was 44%. Univariate analysis showed that primary tumor size, estrogen-receptor negative, progesterone-receptor negative, luminal vs. HER2-positive vs. TNBC, high Ki-67, high densities (cells/mm2) of CD3 CT, CD8+ CT, CD3+ IM, and CD8+ IM cells were associated with a high pCR. ISCR was associated with pCR following NACT. A multivariate model consisting of ISCR and the significant variables from the univariate analysis showed a significant trend for ISCR; however, the low sample size did not provide enough power for the model to be included in this study. Conclusions: These results revealed a significant prognostic role for the spatial distributions of the CD3+, and CD8+ lymphocytes, as well as the ISCR in relation to pCR following NACT.
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The results on the histological class pairs associated with pCR and RD are in line with previously published studies.
“These results are in line with previously published studies [58–66].”
From Digital image analysis and machine learning-assisted prediction of neoadjuvant chemotherapy response in triple-negative breast cancer (2024) · cites this paper as [58]
Results §3.6 reports that two pairs of breast-cancer molecular subtypes—luminal versus HER2-positive and TNBC versus HER2-positive—differed significantly in their association with pCR. This supports the broad claim that prior work found class-pair differences in response, but the paper does not report the citing study’s histological class pairs or a separate analysis of residual disease (RD). (LLM, conf=0.79)
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- Authors
- Rapoport, B. L., Nayler, S., Mlecnik, B., Smit, T., Heyman, L., Bouquet, I., Martel, M., Galon, J., Benn, C.-A., & Anderson, R.
- Affiliations
- Milpark Hospital (ZA)
- University of the Witwatersrand (ZA)
- Inovarion (France) (FR)
- The Medical Oncology Centre of Rosebank (ZA)
- Veracyte, Luminy Biotech Entreprises, 13009 Marseille, France
- Inserm (FR)
- University of Pretoria (ZA)
- Corresponding author
- Rapoport, Bernardo Leon
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2022-05-20
- Volume
- 14
- Issue
- 10
- Pages
- 2525
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC9139282
- OpenAlex
- W4280617720
- Cited by
- 33
- References
- 38
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 8 · 2022: 2
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UpSpace Institutional Repository (University of Pretoria) (submittedVersion, cc-by)
- Funders
- Medical Oncology Centre of Rosebank
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Keywords
- tumor-infiltrating lymphocytes, early breast cancer, triple-negative breast cancer, immune score, CD3+ T cells, CD8+ T cells, pathological complete response, neoadjuvant chemotherapy, prognostic factors, invasive margin, luminal breast cancer, HER2-positive breast cancer
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