The prognostic significance of peritumoral tertiary lymphoid structures in breast cancer

Sofopoulos, Michael; Fortis, Sotirios P.; Vaxevanis, Christoforos; Sotiriadou, Nectaria N.; Arnogiannaki, Niki; Ardavanis, Alexandros; Vlachodimitropoulos, Dimitrios; Perez, Sonia A.; Baxevanis, Constantin N.

doi:10.1007/s00262-019-02407-8

Cited by 90 publications

(78 citation statements)

References 42 publications

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“…In a study conducted by Liu and colleagues, TLSs were significantly associated with favorable DFS in patients with HER2+ breast cancer, independent of TIL status (76). In contrast, a recent analysis of all breast cancer subtypes reported that the presence and density of peritumoral TLSs were not independently associated with DFS and OS (80). Interestingly, TLSs have been demonstrated to be significant predictors of pCR in TNBC patients treated with NAC (78).…”

Section: Tumor-associated Tertiary Lymphoid Structures (Tls)mentioning

confidence: 96%

The Immunology of Hormone Receptor Positive Breast Cancer

et al. 2021

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Immune checkpoint blockade (ICB) has revolutionized the treatment of cancer patients. The main focus of ICB has been on reinvigorating the adaptive immune response, namely, activating cytotoxic T cells. ICB has demonstrated only modest benefit against advanced breast cancer, as breast tumors typically establish an immune suppressive tumor microenvironment (TME). Triple-negative breast cancer (TNBC) is associated with infiltration of tumor infiltrating lymphocytes (TILs) and patients with TNBC have shown clinical responses to ICB. In contrast, hormone receptor positive (HR+) breast cancer is characterized by low TIL infiltration and minimal response to ICB. Here we review how HR+ breast tumors establish a TME devoid of TILs, have low HLA class I expression, and recruit immune cells, other than T cells, which impact response to therapy. In addition, we review emerging technologies that have been employed to characterize components of the TME to reveal that tumor associated macrophages (TAMs) are abundant in HR+ cancer, are highly immune-suppressive, associated with tumor progression, chemotherapy and ICB-resistance, metastasis and poor survival. We reveal novel therapeutic targets and possible combinations with ICB to enhance anti-tumor immune responses, which may have great potential in HR+ breast cancer.

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Section: Tumor-associated Tertiary Lymphoid Structures (Tls)mentioning

confidence: 96%

The Immunology of Hormone Receptor Positive Breast Cancer

et al. 2021

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“…Further studies found that TLSs are associated with increased lymphocyte infiltration into tumors with extended DFS in breast cancer and colorectal cancer ( 191 ). However, the role of TLSs in predicting the prognosis is still under debate because another study of breast cancer showed that patients with abundant TLSs exhibited worse DFS and OS than those lacking TLSs ( 192 ). The cellular component in TLSs has also aroused the interest of scientists.…”

Section: Spatial Architecture Of the Time In Clinical Applicationmentioning

confidence: 99%

Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response

et al. 2021

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Tumors are not only aggregates of malignant cells but also well-organized complex ecosystems. The immunological components within tumors, termed the tumor immune microenvironment (TIME), have long been shown to be strongly related to tumor development, recurrence and metastasis. However, conventional studies that underestimate the potential value of the spatial architecture of the TIME are unable to completely elucidate its complexity. As innovative high-flux and high-dimensional technologies emerge, researchers can more feasibly and accurately detect and depict the spatial architecture of the TIME. These findings have improved our understanding of the complexity and role of the TIME in tumor biology. In this review, we first epitomized some representative emerging technologies in the study of the spatial architecture of the TIME and categorized the description methods used to characterize these structures. Then, we determined the functions of the spatial architecture of the TIME in tumor biology and the effects of the gradient of extracellular nonspecific chemicals (ENSCs) on the TIME. We also discussed the potential clinical value of our understanding of the spatial architectures of the TIME, as well as current limitations and future prospects in this novel field. This review will bring spatial architectures of the TIME, an emerging dimension of tumor ecosystem research, to the attention of more researchers and promote its application in tumor research and clinical practice.

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“…A favorable impact of TLS density on overall survival (OS) and disease-free survival (DFS) of patients has been observed. 62,63,[66][67][68][69][70][71] An important component of TLS are HEV. These are specialized postcapillary venules found in lymphoid tissues that support high levels of lymphocyte extravasation from the blood.…”

Section: Nature Of Immune Cells In Tertiary Lymph Structures In Breastmentioning

confidence: 99%

The Role of Immune Cells in Breast Tissue and Immunotherapy for the Treatment of Breast Cancer

Goff

Danforth

2021

Clinical Breast Cancer

120

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Immune cells are present in normal breast tissue and in breast carcinoma. The nature and distribution of the immune cell subtypes in these tissues are reviewed to promote a better understanding of their important role in breast cancer prevention and treatment. We conducted a review of the literature to define the type, location, distribution, and role of immune cells in normal breast tissue and in in situ and invasive breast cancer. Immune cells in normal breast tissue are located predominantly within the epithelial component in breast ductal lobules. Immune cell subtypes representing innate immunity (NK, CD68 þ , and CD11c þ cells) and adaptive immunity (most commonly CD8 þ , but CD4 þ and CD20 þ as well) are present; CD8 þ cells are the most common subtype and are primarily effector memory cells. Immune cells may recognize neoantigens and endogenous and exogenous ligands and may serve in chronic inflammation and immunosurveillance. Progression to breast cancer is characterized by increased immune cell infiltrates in tumor parenchyma and stroma, including CD4 þ and CD8 þ granzyme B þ cytotoxic T cells, B cells, macrophages and dendritic cells. Tumor-infiltrating lymphocytes in breast cancer may serve as prognostic indicators for response to chemotherapy and for survival. Experimental strategies of adoptive transfer of breast tumor-infiltrating lymphocyte may allow regression of metastatic breast cancer and encourage development of innovative T-cell strategies for the immunotherapy of breast cancer. In conclusion, immune cells in breast tissues play an important role throughout breast carcinogenesis. An understanding of these roles has important implications for the prevention and the treatment of breast cancer.

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The prognostic significance of peritumoral tertiary lymphoid structures in breast cancer

Cited by 90 publications

References 42 publications

The Immunology of Hormone Receptor Positive Breast Cancer

The Immunology of Hormone Receptor Positive Breast Cancer

Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response

The Role of Immune Cells in Breast Tissue and Immunotherapy for the Treatment of Breast Cancer

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