The CD4/CD8 ratio of tumor-infiltrating lymphocytes at the tumor-host interface has prognostic value in triple-negative breast cancer

Wang, Kai; Shen, Tiansheng; Siegal, Gene P.; Wei, Shi

doi:10.1016/j.humpath.2017.09.012

Cited by 83 publications

(61 citation statements)

References 37 publications

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“…Further, high MHCII expression in tumor cells was associated with the presence of tumor-infiltrating lymphocytes (TIL; ref. 9), which are known to be associated with good prognosis in patients with TNBC (10)(11)(12)(13)(14). An independent research team performed IHC on 681 TNBC patient tumors and confirmed that high expression of MHCII in tumor cells was associated with large amounts of tumor-infiltrating CD4-and CD8-positive T cells, and longer DFS (15).…”

Section: Introductionmentioning

confidence: 91%

A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer

et al. 2019

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Approximately 40% of patients with stage I-III triple-negative breast cancer (TNBC) recur after standard treatment, whereas the remaining 60% experience long-term disease-free survival (DFS). There are currently no clinical tests to assess the risk of recurrence in TNBC patients. We previously determined that TNBC patients with MHC class II (MHCII) pathway expression in their tumors experienced significantly longer DFS. To translate this discovery into a clinical test, we developed an MHCII Immune Activation assay, which measures expression of 36 genes using NanoString technology. Preanalytical testing confirmed that the assay is accurate and reproducible in formalin-fixed paraffin-embedded (FFPE) tumor specimens. The assay measurements were concordant with RNA-seq, MHCII protein expression, and tumor-infiltrating lymphocyte counts. In a training set of 44 primary TNBC tumors, the MHCII Immune Activation Score was significantly associated with longer DFS (HR ¼ 0.17; P ¼ 0.015). In an independent validation cohort of 56 primary FFPE TNBC tumors, the Immune Activation Score was significantly associated with longer DFS (HR ¼ 0.19; P ¼ 0.011) independent of clinical stage. An Immune Activation Score threshold for identifying patients with very low risk of relapse in the training set provided 100% specificity in the validation cohort. The assay format enables adoption as a standardized clinical prognostic test for identifying TNBC patients with a low risk of recurrence. Correlative data support future studies to determine if the assay can identify patients in whom chemotherapy can be safely deescalated and patients likely to respond to immunotherapy.Significance: The MHCII Immune Activation assay identifies TNBC patients with a low risk of recurrence, addressing a critical need for prognostic biomarker tests that enable precision medicine for TNBC patients.

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Section: Introductionmentioning

confidence: 91%

A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer

et al. 2019

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“…5E). Significant elevation of CD4/CD8 ratio, which highly correlates with worst prognosis, 31 was also detected in peripheral blood ( Fig. 5F).…”

Section: Chronic Crd Creates An Immunosuppressive Shift In the Tumourmentioning

confidence: 81%

Chronic circadian disruption modulates breast cancer cell stemness and their immune microenvironment to drive metastasis in mice

Hadadi

Taylor

et al. 2019

Preprint

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Breast cancer is the most common type and one of the major causes of cancer death in woman worldwide. Epidemiological studies have established a link between night shift work and increased cancer risk, suggesting that circadian disruption may interfere with carcinogenesis. We aim to shed light on the effect of chronic jetlag on mammary tumour development. Therefore, we used a mouse model of spontaneous mammary tumorigenesis that we exposed to chronic circadian disruption. We observed that circadian disruption significantly increases cancer cell dissemination and metastasis. It also enhances the stemness and tumour-initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. We finally showed that all these defects can be corrected by the use of a CXCR2 inhibitor. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.

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“…The vast majority of recent studies based on single-cell technologies have been focused on CD8+ T cells, as their role in cancer surveillance, editing and control is compelling. However, a role in tumor control is also played by the CD4+ T cell compartment, as reflected by the observation that CD4+ T cells infiltrate the tumor, and by the prognostic value of several CD4 subsets in different malignancies (152)(153)(154). Distinct CD4+ T cells subsets have been described by means of single-cell technologies, including naïve cells, memory-like cells, Th1 cells, Treg, follicular helper T cells (T FH ), and even cytotoxic effector T cells (109,111,121,141,144,146,155,156).…”

Section: Cd4+ T Cellsmentioning

confidence: 99%

Single-Cell Approaches to Profile the Response to Immune Checkpoint Inhibitors

et al. 2020

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Novel treatments based upon the use of immune checkpoint inhibitors have an impressive efficacy in different types of cancer. Unfortunately, most patients do not derive benefit or lasting responses, and the reasons for the lack of therapeutic success are not known. Over the past two decades, a pressing need to deeply profile either the tumor microenvironment or cells responsible for the immune response has led investigators to integrate data obtained from traditional approaches with those obtained with new, more sophisticated, single-cell technologies, including high parameter flow cytometry, single-cell sequencing and high resolution imaging. The introduction and use of these technologies had, and still have a prominent impact in the field of cancer immunotherapy, allowing delving deeper into the molecular and cellular crosstalk between cancer and immune system, and fostering the identification of predictive biomarkers of response. In this review, besides the molecular and cellular cancer-immune system interactions, we are discussing how cutting-edge single-cell approaches are helping to point out the heterogeneity of immune cells in the tumor microenvironment and in blood.

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The CD4/CD8 ratio of tumor-infiltrating lymphocytes at the tumor-host interface has prognostic value in triple-negative breast cancer

Cited by 83 publications

References 37 publications

A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer

A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer

Chronic circadian disruption modulates breast cancer cell stemness and their immune microenvironment to drive metastasis in mice

Single-Cell Approaches to Profile the Response to Immune Checkpoint Inhibitors

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