Emerging Trends in Immunotherapy for Triple Negative Breast Cancer

Dear Colleagues,

Triple negative breast cancer (TNBC) is the most aggressive subtype in women with high rate of metastasis, recurrence, and poor prognosis. The standard treatments of TNBC include neoadjuvant therapy which is administered pre-surgery to assess therapy sensitivity and adapt to post-surgery adjuvant treatment. Although patients respond to these standard treatments, there is a high risk of relapse. Several treatment strategies and novel targets have been developed in the past decades and still ongoing to reduce tumor burden and thus improve the prognosis in TNBC patients.

Immunotherapy for TNBC is evolving rapidly and holds great promise with several agents exhibiting significant potential in improving therapy responses in patients. For instance, immune checkpoint inhibitors and antibodies against highly expressing immune checkpoint molecules-PD1/PDL1, LAG-3, CTLA-4 have been widely explored. Recently, monoclonal antibodies targeting PDL1 such as Atezolizumab, Pembrolizumab and/or combination with chemotherapy have been approved for recurrent unresectable TNBC. Increase in tumor-infiltrating lymphocytes (TILs) are associated with positive response to immunotherapy. Due to high genomic instability and tumor mutation burden in TNBC, the repertoire of TILs is low. Therefore, therapeutic approaches that promote infiltration and re-activation of TILs into tumor tissues have significant impact to promote strong anti-tumor response. Some common immunotherapies include chimeric antigen receptor T (CAR-T) against MUC1, Integrin, TEM8, Mesothelin and so on, monoclonal antibodies or bispecific antibodies (BsAb) against EGFR, VEGFR1, Prolactin receptor etc. as well as the combination of BsAb and CAR-T therapies have been tested and few have been approved for clinical trials. Despite impressive responses towards immunotherapy in early TNBC patients, we still face numerous challenges such as assessment of toxicity to normal tissues, development of more predictive biomarkers and targeted immunotherapies for relapsed tumors, understanding the interaction of tumor-immune cells in tumor microenvironment and specific combination treatments for robust T-cell response in metastatic tumors, that warrants immediate investigation. This Special Issue aims to highlight the basic, translational, and clinical research advancements addressing these concerns in TNBC immunotherapy to improve therapy responses and promote favorable outcome in patients. In this special issue we are inviting original articles/focused reviews on the following research topics:

1. Novel biomarkers or targets of single and combination immunotherapies.
2. Immunotherapeutic developments but not limited to Immune checkpoint inhibitors (ICI), antibodies (monoclonal or bispecific), combination therapy, antibody-drug conjugates, CAR-T, CAR-M or CAR-NK based immunotherapies, neoantigen cancer vaccine, mRNA vaccine.
3. Cytokine and cytokine receptor mediated immunotherapy.
4. Molecular mechanisms of response and resistance to immunotherapy and strategies to overcome immunotherapy resistance.
5. Metabolic markers for immunotherapy.
6. Utility of TILs based immunotherapy- assessment, prognostic value and challenges.
7. Impact of immunotherapy on fertility of pre-menopausal women with TNBC.
8. Impact of immunotherapy on breast cancer tumor microenvironment (tumor-immune cell interactions).
9. Strategies to enhance the efficacy of immunotherapy in early, metastatic, and recurrent TNBC.
10. Assessment and management of immune related toxicity, immune related adverse effects (irAEs), accessibility and efficacy of immunotherapy.

I look forward to receiving your contributions.

Dr. Anjali Geethadevi
Guest Editor

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• triple negative breast cancer
• resistance
• immunotherapy
• biomarkers
• combination therapy
• antibodies
• tumor microenvironment
• immune checkpoint inhibitors
• CAR-T