Relevance of tumor-infiltrating lymphocytes in breast cancer

Dushyanthen, Sathana; Beavis, Paul A.; Savas, Peter; Teo, Zhi L.; Zhou, Chenhao; Mansour, Mariam; Darcy, Phillip K.; Loi, Sherene

doi:10.1186/s12916-015-0431-3

Cited by 199 publications

(257 citation statements)

References 139 publications

(143 reference statements)

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“…These include analyses by hematoxylin/eosin (H&E) staining [12], evaluation of specific subgroups of immune cells by immunohistochemistry, immunofluorescence or flow cytometry [13,14] as well as measuring expression of immune system-related genes [15]. …”

Section: Tumor-infiltrating Lymphocytesmentioning

confidence: 99%

Tumor-Infiltrating Lymphocytes: A Promising Biomarker in Breast Cancer

Loibl

Denkert

2016

Breast Care

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There is clear evidence that the immune system plays an essential role in tumor defense. By determining tumor-infiltrating lymphocytes (TILs), the individual immunological response becomes more apparent and measurable. In breast cancer, high levels of TILs are associated with a more favorable clinical course. In this review, we describe how TILs are determined with emphasis on daily routine diagnostics. We further discuss their impact as a prognostic and predictive biomarker in the neoadjuvant and adjuvant therapy setting as well as in residual disease. We also discuss their potential future implications on further stratifying prognostic subgroups of breast cancer, thereby possibly influencing future therapy considerations.

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Section: Tumor-infiltrating Lymphocytesmentioning

confidence: 99%

Tumor-Infiltrating Lymphocytes: A Promising Biomarker in Breast Cancer

Loibl

Denkert

2016

Breast Care

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“…The immune system plays a vital role in the control of malignant neoplasms, and infiltration of tumors with immune cells correlates with favorable prognosis in several cancer types (1)(2)(3). Immunotherapy is now a major treatment modality in cancer (4)(5)(6)(7)(8), particularly the use of checkpoint inhibitors, which block the interactions used by the tumor to suppress effector T-cell function (9).…”

Section: Introductionmentioning

confidence: 99%

Dual PD-1 and CTLA-4 Checkpoint Blockade Promotes Antitumor Immune Responses through CD4+Foxp3− Cell–Mediated Modulation of CD103+ Dendritic Cells

Beavis

Henderson

Giuffrida

et al. 2018

Cancer Immunology Research

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Immunotherapy is widely accepted as a powerful new treatment modality for the treatment of cancer. The most successful form of immunotherapy to date has been the blockade of the immune checkpoints PD-1 and CTLA-4. Combining inhibitors of both PD-1 and CTLA-4 increases the proportion of patients who respond to immunotherapy. However, most patients still do not respond to checkpoint inhibitors, and prognostic biomarkers are currently lacking. Therefore, a better understanding of the mechanism by which these checkpoint inhibitors enhance antitumor immune responses is required to more accurately predict which patients are likely to respond and further enhance this treatment modality. Our current study of two mouse tumor models revealed that CD4þ

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“…CD8 + T-lymphocytes are critical for tumor-specific adaptive immunity (1). We have previously investigated the clinicopathological and prognostic significance of tumor-infiltrating CD8 + T lymphocytes (TILs) in a large cohort of breast cancers (2).…”

Section: Introductionmentioning

confidence: 99%

Clinical Impact of Tumor DNA Repair Expression and T-cell Infiltration in Breast Cancers

Green

Aleskandarany

Ali

et al. 2017

Cancer Immunology Research

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Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand break repair (BRCA1, BLM, WRN, RECQL4, RECQL5, TOPO2A, DNA-PKcs, Ku70/Ku80), nucleotide excision repair (ERCC1), base excision repair (XRCC1, pol β, FEN1, PARP1), and immune responses (CD8, PD-1, PD-L1, FOXP3) in 1269 breast cancers and validated our findings in an independent estrogen receptor (ER) -cohort (n = 279). Patients with tumors that expressed low XRCC1, low ATM, and low BRCA1 were not only associated with high numbers of CD8 + tumor-infiltrating lymphocyte (TILs), but were also linked to higher grades, high proliferation indexes, presence of dedifferentiated cells, ER -cells and poor survival (all P ≤ 0.01). PD-1 + or PD-L1 + breast cancers with low XRCC1 were also linked to an aggressive phenotype that was high grade, had high proliferation indexes, contained dedifferentiated cells and ER -(all with P values ≤ 0.01) and poor survival (P = 0.00021 and P = 0.00022, for PD-1 + and PD-L1 + cancers, respectively) including in an independent ER -validation cohort (P = 0.007 and P = 0.047, respectively). We conclude that the interplay between DNA repair, CD8, PD-L1, and PD-1 can promote aggressive tumor phenotypes. XRCC1-directed personalization of immune checkpoint inhibitor therapy may be feasible and warrants further investigation in breast cancer.4

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Relevance of tumor-infiltrating lymphocytes in breast cancer

Cited by 199 publications

References 139 publications

Tumor-Infiltrating Lymphocytes: A Promising Biomarker in Breast Cancer

Tumor-Infiltrating Lymphocytes: A Promising Biomarker in Breast Cancer

Dual PD-1 and CTLA-4 Checkpoint Blockade Promotes Antitumor Immune Responses through CD4+Foxp3− Cell–Mediated Modulation of CD103+ Dendritic Cells

Clinical Impact of Tumor DNA Repair Expression and T-cell Infiltration in Breast Cancers

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