# Bacteriotherapy in Breast Cancer
## 2 Bacterotherapy and Enhancing of Human Immunity  
Among the cancer treatments, one therapeutic approach, known as immunotherapy is based on enhancing the host immune system against cancer [25]. There are different strategies used as an inhibitor of immune cells including monoclonal antibodies against tumor antigens, immune checkpoint inhibitors, adoptive cell therapies (e.g., CAR-T cells), and cytokine administration. Some of these strategies are already used in clinical practice for hematological malignancies such as a monoclonal antibody (anti-CCR4 mAb, Mogamulizumab) and a chemokine receptor inhibitor (CXCR4 antagonist AMD3100) [26, 27]. Immunotherapy alters the expression of chemokines receptors in malignancies dictating leukocyte recruitment and activation, angiogenesis, and proliferation in the tumor [28]. Immune checkpoints are known as an important and effective form of immunotherapy that targets cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) [29]. Furthermore, the main aim of the immunotherapy approach is to target the microenvironment of the tumor using the Toll-like receptors (TLRs) agonists that relate to the innate immune activation [30]. Despite the acceptable results, immunotherapy has faced challenges and limitations. One of the main drawbacks of immunotherapy is the lack of efficacy, meaning this approach does not work for every cancer patient and has efficacy only for a few cancers type [31]. Another challenge is that it is difficult to recognize clinically significant biomarkers, known as neoantigens or tumor-specific antigens (TSAs) expressed by tumor cells very slowly. TSAs are produced by normal and tumor cells which result in a lack of specific toxicity and a lower chance of success [25, 31]. Furthermore, more predictive biomarkers are needed because, currently, only a few predictive biomarkers for cancer immunotherapy have been validated [32]. Moreover, heterogeneity within the tumor is another barrier to the success of immunotherapy [32], as well as the development of cancer which are resistant is another reason for therapeutic failures [33]. Additionally, immunotherapy agents are very expensive [34]. Interestingly, host and bacterial (as either pathogen or normal flora) interaction can increase the immune system of the host in various pathways. Tumor cells produce multiple modified surface antigens, reducing immunologic tolerance as carcinogenesis improvements, and various tumor-specific antigens are expressed. Because of the immunosuppressive, the immune response can clear abnormal cells in a two-way direction and a continuous way between the innate and adaptive immunity. In this process, the most important cells are cytotoxic T lymphocytes (T CD8+), natural killer cells (NK) as the main part of the innate immunity, macrophages, dendritic cells (DC), and regulatory T cells (T-reg) FOXP3+. These cells can interact with tumor cells and inhibit their growth. The only effective response for tumor clearance is with T cells. CD8+ T cells have vital roles in the suppression of tumors, and they can kill tumor cells with cytotoxic molecules, such as granzymes and perforin. CD8+ T cells produce IFN\(\gamma\) and increase the expression of MHC class I antigens by the tumor cells, thus, making them better targets for CD8+ T cells. In addition, tumor-infiltrating lymphocytes, in breast cancer, comprise CD4+ T cells specific for class II restricted tumor antigens. Hence, these cells are also able to carry out anticancer activity by providing help to CD8+ T cells or directly recognizing endogenously processed proteins on the surface of cancers eventually followed by secretion of type 1 cytokines or direct tumor killing. Anaerobic bacteria, such as _E. coli_, are potent for the clearance of some tumor cells through stimulation of the host immune system, including lymphocytes T cells, which significantly associates with the antitumor activity.