Cancer and the faults of immunotherapy

Cancer is one of the most prevalent diseases in modern society, yet treatment improvement is slow. The varied forms of cancer, from melanoma to adenocarcinoma, make a panacea nearly impossible. The fact that each cancer is unique makes finding a treatment doubly difficult. Cancer cells are self cells, so it is strenuous to create a treatment where only the cancer is attacked, rather than the entire healthy self. Surgery, chemotherapy, and radiation therapy remain the most common, yet none are 100% effective (American Cancer Society, 2014). A newer approach to cancer treatment is immunotherapy. There are many types of immunotherapy, such as checkpoint inhibitors and monoclonal antibodies (“Immunotherapy”, n.d.). Therapy involving checkpoint inhibitors allows the T cells to start attacking the tumor; therapy with monoclonal antibodies uses antibodies that attach to cancer cells so that the immune system can better see and destroy them. However, the efficacy of these treatments is in question. Only 15%-25% of patients, with various types of cancers, responded positively to monoclonal antibody therapy (Ventola, 2017). One theory regarding the lack of efficacy is that additional checkpoints, as well as other inhibitors of the anticancer immune response, need to be studied. Many trials have been ineffective, due to intense immunosuppression (Weber et al, 2018). Low success rates have been associated with high MDSC levels; 9% of patients with a high MDSC level were progression-free, while about 40% of patients with a low MDSC level had an effective treatment (Figure 2) (Hansen et al, 2015). In order for immunotherapy to become a viable cancer treatment, the manipulation of MDSCs by cancer cells needs to be examined. In this study, this will be studied specifically looking at breast cancer. There has been no significant breakthrough in breast cancer treatment in the past fifteen years, since the inception of the mastectomy in the late 19th century (Plesca et al, 2016). Immunotherapy has been largely ineffective in relation to breast cancer in particular, even though it is extremely effective for melanomas and leukemias, with a 93% remission rate for leukemia patients after immunotherapy (Keown, 2016). The need for improved treatment is apparent and is being studied from many facets.

Breast cancer is best studied through 4T1 cells, mouse breast cancer cells that are syngeneic in nature. 4T1 cells are from balb/c mice, which are essentially homogeneous. Furthermore, these mice have been shown to produce MDSCs, while other mice do not. There are few unknowns in the genome of these mice, making them ideal for this experiment. 4T1 cells metastasize spontaneously once inserted into a mouse. It is also very easy to insert these cells into the appropriate mammary glands. The spread of 4T1 cells is very similar to the spread of breast cancer cells in humans (Pulaski & Ostrand-Rosenberg, 2001). Thus, 4T1 cells are extremely fitting for the study of breast cancer.