# Prognostic relevance of specific TIL (CD4+, CD8+, and FOXP3 + T-cell infiltrates) in triple-negative breast cancer: short- and long-term outcomes

**Authors:** Olga Caramelo, Vânia Almeida, Ana Fidalgo, Augusta Cipriano, Teresa Almeida-Santos

PMC · DOI: 10.1007/s12282-025-01819-y · Breast Cancer (Tokyo, Japan) · 2026-01-07

## TL;DR

This study explores how specific immune cells in triple-negative breast cancer tissues relate to short- and long-term patient outcomes.

## Contribution

The study identifies CD4+ and CD8+ T-cell infiltration as potential biomarkers for predicting prognosis in triple-negative breast cancer.

## Key findings

- High CD4+ T-cell levels are significantly associated with achieving pathological complete response.
- High CD8+ T-cell levels are significantly associated with axillary lymph node negativity.
- Higher levels of CD4+, CD8+, and FOXP3+ T cells show a non-significant tendency toward improved disease-free survival.

## Abstract

Breast cancer is a heterogeneous malignant disease that remains as one of the most prevalent cancers globally. Triple negative breast cancer (TNBC) accounts for 15% of the total of breast cancers and presents high tumor immunogenicity and a tumor microenvironment that plays a critical role in disease progression and patient outcomes.

This study evaluated a total of 30 tissue samples from female patients with TNBC, to characterize specific immune cells within the tumor tissue and investigate their relationship with short (pathological complete response, pCR), long (disease-free survival, DFS) and clinical outcomes. Tumor-infiltrating lymphocytes (TIL) were assessed by immunohistochemistry (IHC) on tissue microarrays (TMA), complemented by digital analysis for standardized quantification.

Our results highlight the influence of CD4⁺ T cells on short-term outcomes: high CD4⁺ T-cell levels were significantly associated with achieving pCR. High CD8⁺ T-cell levels were also significantly associated with axillary lymph node negativity.Regarding long-term outcomes, higher CD4⁺, CD8⁺ and FOXP3⁺ T-cell levels showed a non-significant tendency toward improved DFS.

These findings suggest that high levels of CD4 + T cells and CD8 + T cells are positive predictors of immediate, long-term prognosis and clinical prognosis in patients with TNBC. This study enhances the understanding on the immunological interests in specific subtypes of TIL and identifies potential biomarkers that could drive advancements in precision medicine for breast cancer management.

The online version contains supplementary material available at 10.1007/s12282-025-01819-y.

## Linked entities

- **Proteins:** CD4 (CD4 molecule), CD8A (CD8 subunit alpha), FOXP3 (forkhead box P3)
- **Diseases:** triple-negative breast cancer (MONDO:0005494), breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}
- **Diseases:** TNBC (MESH:D064726), Breast cancer (MESH:D001943), Tumor (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960379/full.md

## References

3 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960379/full.md

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Source: https://tomesphere.com/paper/PMC12960379