Targeting immune checkpoints in breast cancer: an update of early results

Abstract

The immune tumour microenvironment has been shown to play a crucial role in the development and progression of cancer. Expression of gene signatures, reflecting immune activation, and the presence of tumour-infiltrating lymphocytes were associated with favourable outcomes in HER2-positive and triple-negative breast cancer. Recently, immunotherapy with immune checkpoint blockade induced long-lasting responses and improved survival in hard-to-treat malignancies (ie, melanoma and non-small cell lung cancer) and are changing treatment paradigms in a variety of neoplastic diseases. Immune checkpoint blockade has been evaluated in breast cancer, particularly in the triple-negative subtype, with promising results observed in monotherapy or in combination with chemotherapy in the metastatic and neoadjuvant settings. However, identification of patients who are most likely to benefit from immune checkpoint blockade remains challenging, with many patients not responding to treatments and a significant financial cost. The combination of immune checkpoint blockade with conventional cancer treatments such as chemotherapy, radiotherapy, targeted therapies or with other immunotherapies is a promising strategy to potentiate its efficacy in breast cancer although further research is required to effectively identify who will respond to these immunotherapies. In this review we report the most recent results that emerged from trials testing immune checkpoint blockade and potential predictive biomarkers and emphasise the new strategies that are under clinical development in breast cancer.

Intratumoral delivery of CCL25 enhances immunotherapy against triple-negative breast cancer by recruiting CCR9 + T cells

“…Treatment of TNBC remains challenging, because the tumors are highly aggressive and lack therapeutic targets (2, 3). Among the therapeutic options for TNBC, immunotherapy is emerging as a promising approach, but clinical studies in patients with TNBC revealed unsatisfactory outcomes, which is largely attributed to the lack of TILs (36).…”

DNA methylation of immune checkpoints in the peripheral blood of breast and colorectal cancer patients

“…Reports show that, not only immune infiltrating cells, but also circulating cells can possess an immune suppressive phenotype in cancer patients. [14][15][16] We investigated a set of immune checkpoints/ ligands including PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, VISTA and PD-L1 in peripheral blood mononuclear cells (PBMCs) from healthy donors (n = 32), breast cancer patients (n = 31) and colorectal cancer patients (n = 23). Results showed that the expressions of TIM-3, TIGIT and PD-L1 in PBMCs of PBC patients were significantly higher and LAG-3 was significantly lower compared with HD ( Figure 1(c-f)).…”

The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer

“…There is evidence that the low immunogenicity and the intense immunosuppressive tumor microenvironment (TME) of breast cancers (BC) limit the benefit of immunotherapies targeting the adaptive immune system, such as checkpoint inhibitors (CPI) [1,2]. Immunosuppressive mechanisms are essential for the development of normal mammary glands; these strategies are also used by BC cells to promote tumor tolerance and escape from immune surveillance in the early stages of disease, suggesting an important role of adaptive and innate immunity in BC development and progression.…”