Tertiary lymphoid structures: prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer

Lee, Hee Jin; Park, In Ah; Song, In Hye; Shin, Su‐Jin; Kim, Joo Young; Yu, Jong Han; Gong, Gyungyub

doi:10.1136/jclinpath-2015-203089

Cited by 131 publications

(107 citation statements)

References 33 publications

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“…Each of these first three patterns, but not TIL alone, was found to be statistically significant for improved clinical prognosis when using multivariate analysis in a cohort of patients . This recapitulates what was found by Lee et al ,. who showed that “tertiary lymphoid structures” characterized by large lymphoid aggregates in close proximity to the in situ component of triple‐negative breast carcinomas were significantly associated with disease‐free survival as well as when combined with high TIL densities.…”

Section: Discussionsupporting

confidence: 86%

Peritumoral cuffing by T‐cell tumor‐infiltrating lymphocytes distinguishes HPV‐related oropharyngeal squamous cell carcinoma from oral cavity squamous cell carcinoma

Poropatich

Hernández

Fontanarosa

et al. 2017

J Oral Pathology Medicine

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Section: Discussionsupporting

confidence: 86%

Peritumoral cuffing by T‐cell tumor‐infiltrating lymphocytes distinguishes HPV‐related oropharyngeal squamous cell carcinoma from oral cavity squamous cell carcinoma

Poropatich

Hernández

Fontanarosa

et al. 2017

J Oral Pathology Medicine

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“…Pan et al’s study revealed that the percentage of sTILs and density of CD8+ T-lymphocytes were positively correlated with Ki-67 in TNBCs [39]. Lee et al found that TNBCs with higher levels of TILs showed lower LVI [40]. However, the relationships between clinicopathologic characteristics and TILs still need to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Predictive value of tumor-infiltrating lymphocytes to pathological complete response in neoadjuvant treated triple-negative breast cancers

et al. 2018

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BackgroundTriple-negative breast cancers (TNBCs) are a group of heterogeneous diseases with various morphology, prognosis, and treatment response. Therefore, it is important to identify valuable biomarkers to predict the therapeutic response and prognosis for TNBCs. Tumor-infiltrating lymphocytes (TILs) may have predictive value to pathological complete response (pCR) in neoadjuvant treated TNBCs. However, absence of standardized methodologies for TILs measurement has limited its evaluation and application in practice. In 2014, the International TILs Working Group formulated the recommendations of pathologic evaluation for TILs in breast cancers.MethodsTo evaluate the predictive value of TILs scored by methods recommended by International TILs Working Group 2014, we performed a retrospective study of TILs in 166 core needle biopsy specimens of primary invasive TNBCs with neoadjuvant chemotherapy (NAC) in a Chinese population. Intratumoral TILs (iTILs) and stromal TILs (sTILs) were scored respectively. The associations between TILs and pCR were analyzed.ResultsBoth sTILs (p = 0.0001) and iTILs (P = 0.001) were associated with pCR in univariate logistic regression analysis. Multivariate logistic regression analysis indicated that both sTILs (P = 0.006) and iTILs (P = 0.04) were independent predictors for pCR. Receiver operating characteristics (ROC) curve analysis was used to identify the optimal thresholds of TILs. TNBCs with more than 20% sTILs (P = 0.001) or with more than 10% iTILs (P = 0.003) were associated with higher pCR rates in univariate analysis. Multivariate analysis showed that a 20% threshold of sTILs (P = 0.005) was an independent predictive factor for pCR.ConclusionsOur study indicated that TILs scored by recommendations of International TILs Working Group 2014 in pre-NAC core needle biopsy specimens was significantly correlated with pCR in TNBCs, higher TILs scores predicting higher pCR rate. Both sTILs and iTILs were independent predictors for pCR in TNBCs. A 20% threshold for sTILs may be feasible to predict pCR to NAC in TNBCs.

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“…We have previously shown that high TIL levels and high MxA expression in TNBCs were associated with favourable clinical outcomes. 12,22 Conversely, Fumagalli et al 7 have demonstrated that ADAR silencing in breast cancer cell lines (MDA-MB-231, MCF-7 and BT-474) is associated with a statistically significant decrease in cell proliferation and increase in cell apoptosis, suggesting the role of ADAR in cell proliferation and apoptosis. We performed a GSEA study and demonstrated that tumours with high ADRA1 expression are associated with immune responses and the apoptosis pathway.…”

Section: Discussionmentioning

confidence: 99%

ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple-negative breast cancer

et al. 2017

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Tumours with a high mutation burden exhibit considerable neoantigens and tumour-infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope. However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte levels in triple-negative breast cancer have not been well evaluated. We immunohistochemically examined ADAR1 expression in 681 triple-negative breast cancer patients and analysed their clinicopathological characteristics. We also analysed basal-like tumours using The Cancer Genome Atlas data. Among the 681 triple-negative breast cancer patients, 45.8% demonstrated high ADAR1 expression. Tumours with high ADAR1 expression exhibited high tumourinfiltrating lymphocyte levels, considerable CD8 + T lymphocyte infiltration, high histological grade and high expression of interferon-related proteins, including HLA-ABC, MxA and PKR. Among patients with lymph node metastasis, those with high tumour-infiltrating lymphocyte levels and low ADAR1 expression demonstrated the best disease-free survival. The Cancer Genome Atlas data analysis of basal-like tumours revealed significant positive correlation between ADAR1 and CD8B expression and positive association of high ADAR1 expression with immune responses and apoptosis pathways. We detected high ADAR1 expression in half of the triple-negative breast cancer patients. In addition to DNA mutations, RNA editing can be related to neoantigens; hence, we need to explore non-synonymous mutations exclusively found using RNA sequencing data to identify clinically relevant neoantigens.

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Tertiary lymphoid structures: prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer

Abstract: TLSs are frequently present in TNBC and are closely associated with TILs. TILs provide additional prognostic information in patients with TNBC with a higher pTNM stage.

Cited by 131 publications

References 33 publications

Peritumoral cuffing by T‐cell tumor‐infiltrating lymphocytes distinguishes HPV‐related oropharyngeal squamous cell carcinoma from oral cavity squamous cell carcinoma

Peritumoral cuffing by T‐cell tumor‐infiltrating lymphocytes distinguishes HPV‐related oropharyngeal squamous cell carcinoma from oral cavity squamous cell carcinoma

Predictive value of tumor-infiltrating lymphocytes to pathological complete response in neoadjuvant treated triple-negative breast cancers

ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple-negative breast cancer

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