Dataset Information

Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis.

ABSTRACT:

Background

Breast cancer is the most common invasive cancer to affect women in the world. Studies showed tumor-infiltrating lymphocytes can exhibit both beneficial and harmful effects on the biology and clinical outcome of breast cancer, the conclusion still remains incomplete. Here, we conducted a meta-analysis to evaluate the relationship between tumor-infiltrating lymphocytes and breast cancer.

Methods

A comprehensive search strategy was used to search relevant literatures in PubMed and the ISI Web of Science. The correlation among TILs and breast cancer clinicopathological features and prognosis was analyzed by using Review Manager 5.3 and Stata 12.0.

Result

Seventeen eligible studies consisting of 12,968 participants were included. We found that higher value of tumor-infiltrating lymphocytes had no relationship with breast cancer clinicopathological variables. Interestingly, it was correlated with response to neoadjuvant chemotherapy in majority (pooled RR 2.43, 95% CI 1.99-2.97). Moreover, higher value of total tumor-infiltrating lymphocytes (both intraepithelial and stromal) was associated with better prognosis (pooled HR 0.88, 95% CI 0.83-0.94), whereas some subtypes predicted a worse prognosis.

Conclusion

This meta-analysis indicated that high value of total TILs is not associated with breast cancer clinicopathological features, but can predict a favorable outcome for neoadjuvant chemotherapy in majority except for hormone receptor (-) subtype. And higher total TILs (both intraepithelial TILs and stromal TILs) may be the potential better prognostic indicators, while some subtypes like PD-1(+) TILs and Foxp3(+) TILs show a worse prognosis.

SUBMITTER: Yu X

PROVIDER: S-EPMC4823351 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis.

Yu X X Zhang Z Z Wang Z Z Wu P P Qiu F F Huang J J

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 20151012 5

<h4>Background</h4>Breast cancer is the most common invasive cancer to affect women in the world. Studies showed tumor-infiltrating lymphocytes can exhibit both beneficial and harmful effects on the biology and clinical outcome of breast cancer, the conclusion still remains incomplete. Here, we conducted a meta-analysis to evaluate the relationship between tumor-infiltrating lymphocytes and breast cancer.<h4>Methods</h4>A comprehensive search strategy was used to search relevant literatures in P ...[more]

PMID: 26459255

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Project description:BACKGROUND:The objective of this systematic review and meta-analysis was to determine the prognostic value of total tumor-infiltrating lymphocytes (TILs) and subtypes of TILs (CD4+, CD8+, and FOXP3+) in triple-negative breast cancer (TNBC). METHODS:A systematic search of the MEDLINE, EMBASE, and Web of Science databases was conducted to identified eligible articles published before August 2019. Study screening, data extraction, and risk of bias assessment were performed by two independent reviewers. Risk of bias on the study level was assessed using the ROBINS I tool and Quality in Prognosis Studies (QUIPS) tool. We performed a meta-analysis to obtain a pooled estimate of the prognostic role of TILs using Review Manager 5.3. RESULTS:In total, 37 studies were included in the final analysis. Compared to TNBC patients with low TIL levels, TNBC patients with high TIL levels showed a higher rate of pathological complete response (pCR) to treatment (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.43-3.19). With each 10% increase in percentage of TILs, patients with TNBC had an increased pCR (OR 1.09, 95% CI 1.02-1.16). Compared to TNBC patients with low TIL levels, patients with high TIL levels had better overall survival (OS; hazard ratio [HR] 0.58, 95% CI 0.48-0.71) and disease-free survival (DFS; HR 0.66, 95% CI 0.57-0.76). Additionally, with a continuous increase in TIL levels, patients with TNBC had improved OS (HR 0.90, 95% CI 0.87-0.93) and DFS (HR 0.92, 95% CI 0.90-0.95). A high CD4+ TIL level was associated with better OS (HR 0.49, 95% CI 0.32-0.76) and DFS (HR 0.54, 95% CI 0.36-0.80). A high CD8+ TIL level was associated better DFS only (HR 0.55, 95% CI 0.38-0.81), as no statistical association was found with OS (HR 0.70, 95% CI 0.46-1.06). A high FOXP3+ TIL level also was associated with only DFS (HR 0.50, 95% CI 0.33-0.75) and not OS (HR 1.28, 95% CI 0.24-6.88). CONCLUSIONS:TNBC with a high level of TILs showed better short-term and long-term prognoses. High levels of specific phenotypes of TILs (CD4+, CD8+, and FOXP3+) were predictive of a positive long-term prognosis for TNBC.

Project description:BackgroundTumor-infiltrating lymphocytes (TILs) are emerging as strong prognostic factor for early breast cancer patients, especially in the triple-negative subtype. Here, we aim to validate previous findings on the prognostic role of TIL in the context of two randomized adjuvant trials and to investigate whether lymphocyte infiltrates can predict benefit from adjuvant anthracyclines.Patients and methodsA total of 816 patients enrolled and treated at the Gustave Roussy in the context of two multicentric randomized trials comparing adjuvant anthracyclines versus no chemotherapy were included in the present analysis. Primary end point was overall survival (OS). Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of intratumoral (It) and stromal (Str) TIL. Each case was also defined as high-TIL or low-TIL breast cancer adopting previously validated cutoffs.ResultsTIL were assessable for 781 of 816 cases. High-TIL cases were more likely grade 3 and estrogen receptor (ER)-negative (P < 0.001). In multivariate analysis, both continuous It-TIL and Str-TIL were strong prognostic factors for OS [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95 P = 0.003; HR 0.89, 95% CI 0.81-0.96, P = 0.005 for It-TIL and Str-TIL, respectively]. The prognostic effect of continuous TIL was limited to triple-negative and HER2-positive patients. Ten-year OS rates were: 89% and 68% for triple-negative high-TIL and low-TIL, respectively (HR 0.44, 95% CI 0.18-1.10, P = 0.07) and 78% and 57% for HER2-positive high-TIL versus low-TIL, respectively (HR 0.46, 95% CI 0.20-1.11, P = 0.08). Either continuous or binary TIL variables did not predict for the efficacy of anthracyclines. Test for interaction P value was not significant in the whole study population and in subgroups (ER+/HER2-, HER2+, ER-/HER2-).ConclusionsWe confirmed the prognostic role of TIL in triple-negative early breast cancer and suggested a prognostic impact in HER2+ patients as well. Basing on our data, TIL should not be used as a parameter to select patients for anthracyclines chemotherapy.

Project description:PurposeIn colorectal cancer (CRC), whether the immune score can be used to predict the clinical prognosis of the patient has not been completely established. Besides, the prognostic values of tumor-infiltrating lymphocytes (TILs) in different anatomical locations, counting sites, and subtypes have been controversial. The purpose of this meta-analysis is to analyze and determine the prognostic value of TILs indices including TIL subsets, infiltrating sites, and anatomical sites.MethodsRelevant literature was obtained by searching PubMed and Google Scholar. The pooled hazard ratio (HR) of the overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) was computed to investigate the prognostic significance of CD3+, CD8+, CD45RO+, and FOXP3+ T cells.ResultsA total of 22 studies involving 5108 patients were included in the meta-analysis. In CC, based on T cell subtypes analysis, the final results indicated that CD8+ and FOXP3+ infiltrating cells, but not CD3+ T cells were prognostic markers for DFS and OS. In addition, with regard to the counting location of TILs, subgroup analysis revealed that only high FOXP3+ infiltrates in the tumor stroma (ST) were significantly associated with OS (HR = 0.38, 95% confidence interval (CI) = 0.22-0.67, P = 0.0007), whereas in invasive margin (IM), high density of CD3+ infiltrating cells indicated increased DFS (HR = 0.76, 95% CI = 0.62-0.93, P = 0.008). At the tumor center (TC), high CD8+ T cells infiltration was associated with improved DFS (HR = 0.50, 95% CI = 0.38-0.65, P < 0.00001). In RC, whether CSS or OS, high-density TIL was associated with improved prognosis.ConclusionIn a single counting site, high-density TILs reflect favorable prognostic value in CC or RC. For CC, more prospective studies are needed to verify whether different anatomical sites affect the distribution of TILs and thus the prognosis of patients. For RC, further studies should analyze the prognostic value of the immune score.

Project description:Tumor-infiltrating lymphocytes (TILs) are an important histopathologic feature of colorectal cancer that confer prognostic information. Previous clinical and epidemiologic studies have found that the presence and quantification of tumor-infiltrating lymphocytes are significantly associated with disease-specific and overall survival in colorectal cancer. We performed a systematic review and meta-analysis, establishing pooled estimates for survival outcomes based on the presence of TILs in colon cancer. PubMed (Medline), Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to April 2017. Studies were included, in which the prognostic significance of intratumoral tumor infiltrating lymphocytes, as well as subsets of CD3, CD8, FOXP3, CD45R0 lymphocytes, were determined within the solid tumor center, the invasive margin, and tumor stroma. Random-effects models were calculated to estimated summary effects using hazard ratios. Forty-three relevant studies describing 21,015 patients were included in our meta-analysis. The results demonstrate that high levels of generalized TILS as compared to low levels had an improved overall survival (OS) with a HR of 0.65 (p = <0.01). In addition, histologically localized CD3+ T-cells at the tumor center were significantly associated with better disease-free survival (HR = 0.46, 95% CI 0.36-0.61, p = 0.05), and CD3 + cells at the invasive margin were associated with improved disease-free survival (HR = 0.57, 95% CI 0.38-0.86, p = 0.05). CD8+ T-cells at the tumor center had statistically significant prognostic value on cancer-specific survival and overall survival with HRs of 0.65 (p = 0.02) and 0.71 (p < 0.01), respectively. Lastly, FOXP3+ T-cells at the tumor center were associated with improved prognosis for cancer-specific survival (HR = 0.65, p < 0.01) and overall survival (HR = 0.70, p < 0.01). These findings suggest that TILs and specific TIL subsets serve as prognostic biomarkers for colorectal cancer.

Dataset Information

Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis.

Background

Methods

Result

Conclusion

Publications

Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis.

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