Tumor-infiltrating lymphocytes and CD8+ T cells predict survival of triple-negative breast cancer

Vihervuori, H.; Autere, Tuomo-Artturi; Repo, Heli; Kurki, Samu; Kallio, Lila; Lintunen, Minnamaija; Talvinen, Kati; Kronqvist, Pauliina

doi:10.1007/s00432-019-03036-5

Cited by 85 publications

(83 citation statements)

References 56 publications

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“…Studies have proved that TIL levels have a strong prognostic value, which can improve the distant recurrence-free survival, disease-free, and overall survival estimates for TNBC patients treated with adjuvant/neoadjuvant chemotherapy (22,23). Increased TIL levels have been observed to be positively correlated with prolonged survival and increased pathological complete response rates (24)(25)(26). Because of the uneven distribution of TILs within the tumor, TIL levels obtained by biopsy in a specific part of the tumor may not reflect the entire tumor.…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Meng

Huang

et al. 2020

Front. Oncol.

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Objectives: Tumor-infiltrating lymphocytes (TILs) have been identified as a significant prognostic indicator of response to neoadjuvant therapy and immunotherapy for triple-negative breast cancer (TNBC) patients. Herein, we aim to assess the association between TIL levels and mammographic features in TNBC patients. Methods: Forty-three patients with surgically proven TNBC who underwent preoperative mammography from January 2018 to December 2018 were recruited. Pyradiomics software was used to extract 204 quantitative radiomics features, including morphologic, grayscale, and textural features, from the segmented lesion areas. The correlation between radiological characteristics and TIL levels was evaluated by screening the most statistically significant radiological features using Mann-Whitney U-test and Pearson correlation coefficient. The patients were divided into two groups based on tumor TIL levels: patients with TIL levels <50% and those with TIL levels ≥50%. The correlation between TIL levels and clinicopathological characteristics was assessed using the chi-square test or Fisher's exact test. Mann-Whitney U-test and Pearson correlation coefficient were used to analyze the statistical significance and Pearson correlation coefficient of clinical pathological features, age, and radiological features. Conclusion: Mammography features not only distinguish high and low TIL levels in TNBC patients but also can act as imaging biomarkers to enhance diagnosis and the response of patients to neoadjuvant therapies and immunotherapies.

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Section: Discussionmentioning

confidence: 99%

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Meng

Huang

et al. 2020

Front. Oncol.

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“…CD8+T cell played a direct and clear role on tumor cell (Giese, Hind & Huttenlocher, 2019;Okada et al, 2020;Taya et al, 2020). Previous studies showed that CD8+T cell infiltration improved a survival benefit of the patient with advanced cancer (Vihervuori et al, 2019). While activated, CD8+T cell induced tumor cell to express some factor to recruit macrophage, which weakened the efficacy of PDCD1 immunotherapy (Neubert et al, 2018).…”

Section: Infiltration Levelmentioning

confidence: 99%

The nine ADAMs family members serve as potential biomarkers for immune infiltration in pancreatic adenocarcinoma

Liu

Dong

et al. 2020

PeerJ

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Background The functional significance of ADAMs family members in the immune infiltration of pancreatic adenocarcinoma (PAAD) awaits elucidation. Methods ADAMs family members with significant expression were identified among differentially expressed genes of PAAD based on The Cancer Genome Atlas (TCGA) database followed by a verification based on the Oncomine database. The correlation of ADAMs in PAAD was estimated with the Spearman’s rho value. The pathway enrichment of ADAMs was performed by STRING and GSEALite, respectively. The protein–protein interaction and Gene Ontology analyses of ADAMs and their similar genes were exanimated in STRING and visualized by Cytoscape. Subsequently, the Box-Whisker plot was used to show a correlation between ADAMs and different tumor grade 1/2/3/4 with Student’s t-test. TIMER was applied to estimate a correlation of ADAMs expressions with immune infiltrates and immune checkpoint blockade (ICB) immunotherapy-related molecules. Furthermore, the effect of copy number variation (CNV) of ADAMs genes was assessed on the immune infiltration levels. Result ADAM8/9/10/12/15/19/28/TS2/TS12 were over-expressed in PAAD. Most of the nine ADAMs had a significant correlation. ADAM8/12/15/19 expression was remarkably increased in the comparison between grade 1 and grade 2/3 of PAAD. ADAM8/9/10/12/19/28/TS2/TS12 had a positive correlation with almost five immune infiltrates. ADAM12/19/TS2/TS12 dramatically related with ICB immunotherapy-related molecules. CNV of ADAMs genes potentially influenced the immune infiltration levels. Conclusion Knowledge of the expression level of the ADAMs family could provide a reasonable strategy for improved immunotherapies to PAAD.

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“…The prognostic and predictive value of tumor-in ltrating lymphocytes (TILs) in breast cancer has been extensively studied in recent years, especially in triple negative and human epidermal growth factor receptor 2-enriched (HER2+) subtypes (1)(2)(3). High TIL levels, which seem to re ect favorable host antitumor immune responses, have been associated with improved clinical outcomes, increased rates of pathological complete response (pCR) to neoadjuvant therapy, and greater bene t from adjuvant therapy in triple negative breast cancers (TNBC) and HER2 + breast cancers (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to overall TIL levels, speci c immune cells have also been associated with survival and therapeutic responses. In particular, extensive tumor-in ltrating cytotoxic CD8 positive (CD8+) Tcells were strongly associated with patients' favorable survival and increased rates of pCR in response to neoadjuvant therapy (3,(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Tumor-infiltrating Lymphocytes in Premenopausal, Luminal Breast Cancer Treated with Adjuvant Endocrine Therapy

Zhang¹,

Abubakar²,

Yuan³

et al. 2020

Preprint

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BackgroundTumor-infiltrating lymphocytes (TILs) have strong prognostic values in triple-negative and HER2-enriched breast cancer, but their prognostic roles in luminal breast cancer (LBC) are less clear. Here, we assessed the overall TILs levels and CD8+ T-cells in relation to the prognosis of LBC patients from China.Methods A total of 596 patients with LBC who were premenopausal and treated with adjuvant endocrine therapy were included. Among them, 160 cases were evaluated for CD8 by immunohistochemical (IHC) staining. Whole-section hematoxilyn and eosin and IHC staining were visually assessed for stromal TILs (sTILs), stromal CD8+ T-cells (sCD8) and intratumoral CD8+ T-cells (iCD8). Multivariable Cox proportional hazards model were used to test the associations between TILs and disease-free survival (DFS) and overall survival (OS) with the adjustment of clinicopathologic characteristics and treatment. ResultsHigh sTILs (≥10%) were associated with high histologic grade (p<0.001), luminal B/HER2- (p<0.001), luminal B/HER2+ subtype (p=0.002), and high Ki67 expression (≥25%; p=0.014). Similar associations were observed for sCD8 but not for iCD8. While sTILs and sCD8 were not associated with either DFS or OS, the presence of iCD8 (≥1%) was associated with better DFS in both univariate (HR=0.51, 95%CI 0.26-0.96, p=0.042) and multivariate (HR=0.48, 95%CI 0.25-0.92, p=0.027) analyses. Similar but less significant associations were found for iCD8 and OS (adjusted HR=0.35, 95%CI 0.11-1.10, p=0.073).Conclusions Among Chinese premenopausal patients with LBC, iCD8 demonstrated suggestive associations with favorable outcomes. In contrast, although sTILs and sCD8 were associated with more aggressive tumor features, they did not appear to be associated with clinical outcomes.

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Tumor-infiltrating lymphocytes and CD8+ T cells predict survival of triple-negative breast cancer

Cited by 85 publications

References 56 publications

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

Correlation Between Mammographic Radiomics Features and the Level of Tumor-Infiltrating Lymphocytes in Patients With Triple-Negative Breast Cancer

The nine ADAMs family members serve as potential biomarkers for immune infiltration in pancreatic adenocarcinoma

Prognostic Significance of Tumor-infiltrating Lymphocytes in Premenopausal, Luminal Breast Cancer Treated with Adjuvant Endocrine Therapy

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