Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes

Stanton, Sasha E.; Adams, Sylvia; Disis, Mary L.

doi:10.1001/jamaoncol.2016.1061

Cited by 449 publications

(335 citation statements)

References 42 publications

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“…Finally, we should acknowledge the possibility that other immunohistochemistry (IHC) based markers or combinations thereof could offer superior predictive information, since immune cells exist in a continuum and the dichotomous categorization does not take into account the plasticity that T lymphocytes and macrophages exhibit, while their relative abundances, such as the CD8+/FOXP3+ ratio, could also offer further predictive and prognostic information. 26 …”

Section: Discussionmentioning

confidence: 99%

Dynamic evaluation of the immune infiltrate and immune function genes as predictive markers for neoadjuvant chemotherapy in hormone receptor positive, HER2 negative breast cancer

et al. 2018

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Gene expression (GE) signatures and Tumor Infiltrating Lymphocytes (TIL) enumeration are predictive for response to neoadjuvant chemotherapy in HR- and in HER2+ breast cancer, but data are conflicting in HR+/HER2- disease. This study aimed to explore their predictive value in this subset, measured both at baseline and after short exposure to chemotherapy. Specifically, the PROMIX phase 2 trial enrolled patients with locally advanced HER2- BC to receive six cycles of epirubicin and docetaxel, plus bevacizumab during cycles 3–6. Patients underwent tumor biopsies at baseline and after cycle 2 for GE profiling and enumeration of TIL, FOXP3+ T-cells and CD163+ macrophages. An immune related gene module and the quantification of the immune infiltrate were analyzed for association with pathologic complete response (pCR), decrease in tumor size and disease-free survival (DFS). Of the 150 patients enrolled in PROMIX, 113 were HR+/HER2-. Baseline GE and immune cell enumeration data were available from 71 patients, while data after 2 cycles of chemotherapy were available from 41. At baseline, only GE was statistically significantly associated with higher pCR rates (OR 2.29, 95% CI 1.05 – 5.38, p = 0.037) and decrease in tumor size (r = 0.25, p = 0.047). In contrast, longitudinal data indicate that both GE (r = 0.54, p<0.001) and TIL abundance (p = 0.009) are stronger predictors for the reduction of tumor size, while low FOXP3+ was statistically significantly associated with an improved DFS (p = 0.027). In conclusion, GE analysis, TIL and FOXP3+ enumeration after short-term exposure to chemotherapy carry important predictive information in HR+/HER2- breast cancer at the neoadjuvant setting.

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Section: Discussionmentioning

confidence: 99%

Dynamic evaluation of the immune infiltrate and immune function genes as predictive markers for neoadjuvant chemotherapy in hormone receptor positive, HER2 negative breast cancer

et al. 2018

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“…Lymphocytes are key mediators of immune surveillance and immune editing, and lymphocyte infiltration into the tumor microenvironment is a prerequisite for an immunologic antitumor reaction. High lymphocyte counts and infiltration of tumors by type I lymphocytes with greater dimensions are associated with a good prognosis in cancers such as colon, ovarian, lung, and breast cancer [51][52][53] . Figure 4.…”

Section: Discussionmentioning

confidence: 99%

The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis

Sun

et al. 2017

Climacteric

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Objectives: The platelet-to-lymphocyte ratio (PLR) is a predictive clinical biomarker for different cancers. However, the results of several studies investigating the association between the PLR and the prognosis of ovarian cancer have been inconclusive. Therefore, there is a need to conduct a metaanalysis to estimate the prognostic value of the PLR in ovarian cancer. Methods: We searched the EMBASE, Medline, PubMed, and Web of Science databases to identify clinical studies that had evaluated the association between the PLR and ovarian cancer prognosis. Outcomes evaluated included overall survival (OS) and progression-free survival (PFS). We also analyzed PLR differences between malignant ovarian masses and the controls. Results: Twelve relevant studies that comprised 2340 patients were selected for the meta-analysis. The results revealed that elevated PLR was significantly associated with poor OS (hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.05-2.56, p < 0.01) and PFS (HR 1.61, 95% CI 1.03-2.51, p < 0.01). The PLRs in malignant cases were higher than in controls (mean difference ¼ 63.57, 95% CI 39.47-87.66, p < 0.00001). Conclusion: An elevated PLR is associated with poor prognosis in patients with ovarian cancer. The PLR could be employed as a prognostic marker in patients with ovarian cancer. ARTICLE HISTORY

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“…It has been suggested that the immune response in invasive breast cancer and other tumor types may correlate with mutational load due to the potential for neoantigen formation (4) or, alternatively, with the specific mutational signature (5). Higher TILs are consistently seen in triple-negative breast cancers, followed by HER2-positive cancers, with high TIL scores observed only rarely in luminal cancers (6).…”

Section: Introductionmentioning

confidence: 99%

Relationship of the Breast Ductal Carcinoma In Situ Immune Microenvironment with Clinicopathological and Genetic Features

Hendry

Pang

Byrne

et al. 2017

Clinical Cancer Research

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Purpose: The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown.Experimental Design: We quantified tumor associated lymphocytes (TIL) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases, respectively), some of which had copy number (n ¼ 55) and mutation data (n ¼ 20).Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range, 0%-90%). Most DCIS were negative for tumor cell PD-L1 staining (89%), but 25% of cases were positive for immune cell staining. We observed that, as in invasive breast cancer, TILs and PD-L1 positivity were significantly greater in high-grade (P ¼ 0.002/0.035), ER-negative (P ¼ 0.02/0.02), and ERBB2-amplified tumors (P < 0.001/0.048). Comedo necrosis was significantly positively associated with TILs (P < 0.0001) but not with PD-L1. The TILs score was significantly higher in cases with TP53 mutation (P ¼ 0.03) but not with PIK3CA or GATA3 mutation. In the cases with copy number data, both the fraction of the genome altered and the number of telomeric imbalances were significantly positively correlated with TILs (both P < 0.001). This result strongly contrasted with invasive breast cancer data, where aneuploidy was not correlated to TIL levels.Conclusions: Although a small cohort, our data suggest a preliminary model by which the progression of DCIS to invasive carcinoma may involve an altered relationship of tumor copy number with the immune microenvironment, possibly by the immunoediting of the tumor. Clin Cancer Res; 23(17); 5210-7.Ó2017 AACR.

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Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes

Abstract: The magnitude of TIL is variable within and between breast cancer subtypes. Levels of lymphocytic subpopulations may identify breast cancers more amenable to immunomodulation and indicate additional strategies to enhance immunity in patients with low to moderate levels of TILs.

Cited by 449 publications

References 42 publications

Dynamic evaluation of the immune infiltrate and immune function genes as predictive markers for neoadjuvant chemotherapy in hormone receptor positive, HER2 negative breast cancer

Dynamic evaluation of the immune infiltrate and immune function genes as predictive markers for neoadjuvant chemotherapy in hormone receptor positive, HER2 negative breast cancer

The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis

Relationship of the Breast Ductal Carcinoma In Situ Immune Microenvironment with Clinicopathological and Genetic Features

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