Advances in Targeting Immune Checkpoint Inhibitors and New Vaccination Strategies for Triple-negative Breast Cancers:...

Triple-negative breast cancers (TNBCs) are a type of breast cancer (BC) characterized by the absence of ER, PR, and HER2 expression. They account for 10-15% of invasive BC cases and are known for being aggressive and highly metastatic. TNBC patients face limited effective treatment options due to the inherent heterogeneity of the disease and a lack of targetable receptor molecules.

Chemotherapy, used as part of neoadjuvant or adjuvant therapy, remains the major treatment recourse but is associated with toxicity, resistance, and relapse. Unlike other BCs, TNBCs' tumor microenvironment (TME) features many tumor-associated antigens (TAAs) and significant lymphocyte infiltration, such as Tc cells and other immune cells, e.g., NK cells. The collection of relevant studies herein was done by typing the keywords "Targeted Immunotherapy for Triple Negative Breast Cancer" on Google and PubMed databases, which were henceforth retrieved with a focus on recent attempts.

TNBCs are considered immunologically "hot". However, the presence of significant immunosuppressive cells, including Tregs, TAMs, and MDSCs, along with inhibitory cytokines, such as IL- 10 secreted by these cells, expression of immunosuppressive molecules, such as PD-1, PD-L1, and CTLA-4, weakens the anti-tumor response through immunosuppressive actions.

TNBC-TME is a target for immunotherapy. Current immunotherapeutic strategies target the TNBC TME using immune checkpoint inhibitors (ICIs) against PD-1, PD-L1, and CTLA-4. Additionally, several studies focus on developing vaccines targeting immunosuppressive cells and molecules of the TNBC TME.

This review highlights advancements in immunotherapy strategies for mitigating TNBC, with a particular focus on targeting immunosuppressive molecules.