**1. Introduction**

Triple negative breast Cancer (TNBC), is an aggressive breast cancer subtype characterized by the lack of hormone receptors; estrogen receptor, progesterone receptor and HER2 receptor accounting for about 15–20% of all breast cancers, with chemotherapy available as the prime systemic therapy. The treatment results into low median overall survival with earlier recurrence and metastasis posing to be a great hurdle in the control of this disease [1]. Therefore, improved therapies are urgently needed. Immunotherapy has prolonged survival in other solid tumors and represents a promising treatment strategy for TNBC (**Figure 1**). In the recent days, targeting immune checkpoint inhibitors are noted immunotherapeutic agents that are known to block immunosuppressive receptors like PD-1 (anti-programmed

#### **Figure 1.**

*Represents the available treatments for TNBC (triple negative breast cancer).*

death receptor-1) and CTLA-4 (cytotoxic T lymphocyte antigen-4), which are significantly involved in tumor directed immune responses [2]. Moreover, several characteristics of TNBC make immunotherapy to be corner stone of the modern therapeutic regimens such as the presence of TILs (Tumor infiltrating Lymphocytes (TILs). The TILs are associated with better therapeutic responses increasing the disease free survival and overall prognosis in TNBC in comparison to other breast cancer subtypes. The presence of TILs as well acts as predictive biomarkers for immunotherapy response that makes immunotherapy more intriguing for TNBC treatment [3–5]. Besides, TNBC are known to possess higher PD-L1 expression levels on both tumoral and immune cells that are likely to respond to the immune checkpoint inhibitors (ICIs) such as pembrolizumab, nivolumab (monoclonal antibodies against PD-1), Ipilimumab (antibody against CTLA-4) and Atezolizumab, Avelumab (antibody against PD-L1) [2, 6, 7]. In addition, the presence of significant number of non-synonymous mutations in TNBC generate neo-antigens specific to tumors that activate robust anti-tumor immune responses that can be synergistically utilized by the current immunotherapeutic agents like ICIs [8–10]. Nevertheless, the presence of higher levels of BRCA1 and BRCA2 mutations giving rise to unstable genetics acts as a significant predictive marker for immunotherapy response [11].

The immune system plays a dual role in a way that it not only is involved in tumor initiation and progression but also acts significantly in the recognition and destruction of cancer cells. The later generates a tumor-directed immune response involving cytotoxic T lymphocytes [12, 13]. For cancer progression the tumors are known to evade the anti-tumor immune response by certain array of mechanisms like activation of pro-tumor-polarized innate inflammatory cells, activation of humoral immunity, suppression of tumor-specific antigens, infiltration by Th2 T cells, absence of major histocompatibililty complexes (MHC) on tumor cell surface and negative immune checkpoint inhibitor expression by tumor cells [13, 14]. These mechanisms followed by tumor cells to evade immune responses are known as hallmarks of cancers as these work in concordance to suppress the anti-tumor response and promote cancer progression. Therefore, in order to bring cancer control strategies targeting these specific mechanisms are utilized in immunotherapy to bring in control the tumor progression (**Figure 2**) [15].

*Integrating Immunotherapy with Chemotherapy: A New Approach to Drug Repurposing DOI: http://dx.doi.org/10.5772/intechopen.100183*

#### **Figure 2.**

*Overview of involvement of immune system in TNBC with combination treatment options; A. Represents on recognition of the antigen from the tumor cell the immune cell destroying the tumor cell B. Shows that how PD-L1 from the tumor cell interacts with PD-1 and this binding causes T cell exhaustion and helps the tumor cell evading the immune response.*

Therefore, actively manipulating the immune system for TNBC treatment represents to be an attractive strategy as this particular breast cancer subtype has lacked in terms of extensive clinical management. In view of that, immune checkpoint inhibitors (ICIs) has revealed promising results in TNBC patients by substantial improvement in TNBC patients overall prognosis. However, the focus of this field is to recognize the immunogenic identity of patients for the clinical management of patients and in specific to identify specific therapeutic agents to target tumor microenvironment [14]. Nevertheless, the utilization of current therapeutics like chemotherapy, radiotherapy in combination with immunotherapy will augment the immunotherapeutic response as they enhance tumors mutational load, downregulate immune suppression by tumor microenvironment and boost antigen presentation by tumor cells, henceforth making tumors more prone to immunotherapy (**Figure 2**) [16–18]. Interestingly, many clinical trials are underway and some have revealed that combination of immunotherapy with other therapeutic agents besides chemotherapy and radiotherapy has enhanced the patient responses in terms of progression free survival and standard of care [19, 20].
