Abstract 1399: The role of CCN5 in regulation of tumor-infiltrating lymphocytes (TILS) in triple-negative breast cancer (TNBC) cells

Abstract TNBC accounts for about 15-20 percent of all breast cancer cases, with a high incidence in young and African-American women. TNBC lacks the expression of estrogen receptor, progesterone receptor, and normal human epidermal growth factor receptor type 2 (HER2) copy number with expression. Thus, TNBC is not sensitive to endocrine and targeted molecular therapies. Therefore, surgery and systemic chemotherapy are the primary treatment methods for TNBC. The adjuvant therapy regimen includes anthracycline, paclitaxel, or both in (Neo-) early TNBC. However, this treatment is often ineffective after recurrence or metastasis. Therefore, continuously searching for new targeted therapies and immunotherapies becomes a focus in TNBC treatment in patients with diverse communities. The studies showed that TNBC is more immunogenic than other subtypes of breast cancers with tumor-infiltrating lymphocytes (TILs) in its microenvironment. More importantly, Cytotoxic CD8+ TILs of the adaptive immune system are the most potent effectors in the anticancer immune response and constitute the backbone of cancer immunotherapy. Therefore, a high number of CD8+TILs in TNBC patients' tumors are considered a better prognosis following neoadjuvant chemotherapy. Hence, increasing and activating CD8+ TILs could be an exciting and appropriate approach to treating TNBC. Blocking immune checkpoints can inverse the microenvironment immunosuppressive state and enhance the function of tumor cell clearance. One of the major immune checkpoint therapies has involved a monoclonal antibody against programmed cell death-1 (PD-1) /programmed cell death-ligand 1 (PD-L1), expressed in various tumor cells, including TNBC and immune cells. The studies found that PD-1/PD-L1 negatively regulates CD8+ TILs in cancers, and blockade of PD-1 can induce CD8+ TILs responses in advanced melanoma. Interestingly, PD-1/PD-L1 immunotherapy has also progressed in suppressing TNBC growth and progression. However, the currently available immune checkpoint therapies have therapeutic limitations with the toxicity of the drugs. Thus, new therapeutic options are urgently needed. Our studies found that the expression of CCN5, an anti-invasive gene, correlates with the number of cytotoxic CD8+ TILs in ER+ and HER-2 positive breast cancer samples. Furthermore, we also observed that PD-L1 (programmed death-ligand 1), which was found to have high and low expression in MDA-MB-231 and 4T1, respectively, was suppressed in MDA-MB-231 and 4T1 TNBC cell lines by CCN5 recombinant protein treatment for 48 h. These findings might provide a novel immune checkpoint mechanistic explanation of CCN5 that mediates TNBC growth and progression suppression. Citation Format: Upasana Biswas, Anjali Kambhampati, Noor Haideri, Archana De, Sunil Upadhyay, Snigdha Banerjee, Sushanta Banerjee. The role of CCN5 in regulation of tumor-infiltrating lymphocytes (TILS) in triple-negative breast cancer (TNBC) cells abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 1399.