Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis

Gao, Zhiqiang; Li, Cun-xin; Liu, Ming; Jiang, Jianhai

doi:10.1186/s12885-020-07654-y

Cited by 86 publications

(87 citation statements)

References 44 publications

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“…In early TNBC patients treated with anthracycline-based adjuvant chemotherapy, the levels of TILs are positively correlated with a better outcome [ 45 ]. Similar results were obtained for untreated early TNBCs, showing that higher TIL densities correlated with better survival [ 46 , 47 ]. Similarly, high quantities of cytotoxic CD8+ TILs are positively associated with a longer survival of early TNBC patients [ 48 ] and better response to neoadjuvant chemotherapy [ 49 ].…”

Section: Discussionsupporting

confidence: 75%

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

Boissière

Jacot

Massol

et al. 2021

Cancers

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Chemokines and their receptors are key players in breast cancer progression and outcome. Previous studies have shown that the chemokine receptor CXCR2 was expressed at higher levels by cells of the tumor microenvironment in triple-negative breast cancers (TNBCs). The aim of this study was to focus our attention on a retrospective cohort of 290 TNBC cases and analyze the involvement of CXCR2, CD11b (a marker of granulocytes) and CD66b (a marker of neutrophils) and their link with immune infiltration and immune checkpoint markers. We report that high densities of CXCR2-, CD11b- and CD66b-positive cells were associated with high-grade tumors. Moreover, molecular apocrine TNBCs, defined here as tumors that express both AR and FOXA1 biomarkers, exhibited low levels of CXCR2 and CD11b. High CXCR2 and CD11b levels were correlated with elevated density of tumor-infiltrating lymphocytes (TILs), CD8+ cytotoxic lymphocytes, expression of PD-L1 by tumor and stromal cells and of PD-1 by stromal cells. On the other hand, CD66b levels were associated only with CD8+, stromal PD-L1 and PD-1 expression. In univariate analysis, low levels of CXCR2 were correlated with poor OS and RFS. In multivariate analysis, low levels of CXCR2 were associated with poor OS. Finally, in TNBC treated with adjuvant chemotherapy, CXCR2 density was associated with longer RFS. Overall, our data highlight the potential beneficial association of high levels of CXCR2 with a subgroup of TNBC patients characterized by a better prognosis.

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Section: Discussionsupporting

confidence: 75%

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

Boissière

Jacot

Massol

et al. 2021

Cancers

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“…While increased TILs were associated with a survival benefit in HER2-positive and TNBC, in luminal/HER2-negative tumors high TIL was a negative prognostic factor, raising the question of the role played by the immune system in these tumors. Similar results were reached by Gao et al and Waks et al, analyzing the association between pCR and survival, and TILs in HR+ BC [67,68]. Further, another issue is how achieving a pathological complete response (pCR) correlates with long-term outcome in HR+ HER2-negative BC.…”

Section: Clinical Significance Of Tumor-infiltrating Lymphocytes In Hr+ Bcsupporting

confidence: 79%

Luminal Breast Cancer: Risk of Recurrence and Tumor-Associated Immune Suppression

Pellegrino

Hlavatá²,

Migali

et al. 2021

Mol Diagn Ther

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Hormone-receptor positive (HR+) breast cancer (BC) (including the luminal A and the luminal B subtypes) is the most common type of tumor in women diagnosed with early-stage BC (EBC). It represents a highly heterogeneous subgroup that is characterized by different risks of relapse. The aim of this review is to discuss the possible role played by the immune response in predicting this risk, along with the most common clinical and pathological factors and molecular tools that have been developed and are already in use. As opposed to what has previously been observed in the most aggressive human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC) subtypes, a high proportion of tumor-infiltrating lymphocytes (TILs)-reflecting a spontaneous and pre-existing immune response to the tumor-has been linked to a worse prognosis in HR+ EBC. This work provides some immune biological rationale explaining these findings and provides the basics to understand the principal clinical trials that are testing immunotherapy in HR+ (luminal) BC.Antonino Musolino and Cinzia Solinas contributed equally to this work.

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“…TILs, the foremost mononuclear immune cells infiltrating the tumor microenvironment, and are strongly associated with breast cancer prognosis 2 . In patients treated with NAC, the pooled analysis showed that high TIL levels could predict pathological response in all breast cancer subtypes and were associated with longer DFS in the TNBC and HER2 + but not the luminal‐HER2 − subtype 3,8 . Our study confirmed that a high pre‐NAC TIL level was significantly associated with higher pCR rates in the whole population regardless of molecular subtype.…”

Section: Discussionsupporting

confidence: 73%

“…The level of tumor‐infiltrating lymphocytes (TILs) is a foremost immunobiological marker and can be classified as stromal or intra‐tumoral 2 . The presence of abundant TILs is significantly correlated with superior survival in patients with human epidermal growth factor receptor 2 (HER2)–enriched or triple‐negative breast cancer (TNBC), and studies have revealed that the stromal TIL level is a better biomarker than the level of intra‐tumoral TIL 2,3 …”

Section: Introductionmentioning

confidence: 99%

Association of tumor‐infiltrating lymphocytes before and after neoadjuvant chemotherapy with pathological complete response and prognosis in patients with breast cancer

Jiang

Fei

et al. 2021

Cancer Medicine

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Purpose To evaluate the predictive and prognostic value of tumor‐infiltrating lymphocytes (TILs) before and after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Patients and methods Consecutive breast cancer patients treated with NAC between August 2008 and November 2019 were retrospectively analyzed. TIL levels were evaluated of invasive tumor samples, and high expression was defined as TILs >10%. Total pathological complete response (pCR) was defined as no invasive tumor in the breast or lymph nodes. Univariate and multivariate analyses were used to assess factors associated with pCR rate, disease‐free survival (DFS), and overall survival. Results A total of 461 patients were included. The mean pre‐NAC TIL level was higher among patients with pCR than among patients without pCR (24.28% ± 2.34% vs. 11.34% ± 0.60%, respectively, p < 0.0001). The multivariate analysis demonstrated that a high pre‐NAC TIL level was an independent risk factor for a higher pCR (odds ratio = 3.92, 95% CI = 2.23–6.90, p < 0.001). Patients with high pre‐NAC TIL levels had a better 5‐year DFS than those with low pre‐NAC TIL levels (84.5% vs. 68.9%, HR = 0.50, 95% CI = 0.31–0.81, p = 0.005). The multivariate analysis showed that pre‐NAC TIL (HR = 0.48; 95% CI = 0.29–0.81, p = 0.006) but not post‐NAC TIL (HR = 0.89, 95% CI = 0.50–1.59, p = 0.699) was significantly associated with DFS among patients without pCR. Furthermore, patients with low pre‐ and post‐NAC TIL levels had a worse 5‐year DFS than those with high pre‐NAC TIL levels (HR = 2.09, 95% CI = 1.23–3.56, p = 0.007). Conclusions Pre‐NAC TIL level can predict pCR and DFS in patients with breast cancer receiving NAC. For patients without pCR, pre‐NAC TIL, and TIL category change, but not post‐NAC TIL, were significantly associated with DFS.

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Predictive and prognostic role of tumour-infiltrating lymphocytes in breast cancer patients with different molecular subtypes: a meta-analysis

Cited by 86 publications

References 44 publications

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

Luminal Breast Cancer: Risk of Recurrence and Tumor-Associated Immune Suppression

Association of tumor‐infiltrating lymphocytes before and after neoadjuvant chemotherapy with pathological complete response and prognosis in patients with breast cancer

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