Yukta Kulkarni ’22
Cancer is a disease in which there is uncontrollable cell growth in any part of the body. The migration of the cancer cells from the origin to other parts of the body is called metastasis, causing malignant tumors. Cancerous cells can be aided by other cells found in tissues such as tumor-associated macrophages (TAMS) that stimulate tumor growth, prompt metastasis, and promote the evasion of tumors from the immune system and medications/therapies. However, due to technological advances, it is possible to reprogram the innate function of cells. In the past, researchers have reprogrammed the cell using polarized macrophages with receptors activating immunity that suppressed colon cancer in mice. With these recent findings, L. Sun and their team of researchers wanted to determine if a fusion of MPLA (a lipid that advances the body’s immune response) and IFNy (a protein that promotes macrophage activation) could elicit control over metastatic breast and lung cancer in mice.
The researchers first determined if the MPLA+IFNy mixture could reprogram TAMS to be tumoricidal, or able to kill tumor cells. When injecting MPLA or IFNy alone, no cancer cells were destroyed. However, forty-eight hours after isolating tumor cells from mice breasts and injecting them with the mixture, around 90% of the tumor cells died. The MPLA+IFNy together secrete macrophages which activate cytotoxic T cells that kill tumor cells. With the in vitro experiment showing success, the researchers tested the combination in vivo in mice breast and lung tumors. After injections into the tumor, MPLA+IFNy showed to halt tumor growth in both cancers. Since intratumoral injections aren’t the standard treatment, the mixture was tested intraperitoneally, a more common treatment. Higher doses of MPLA+IFNy needed to be injected for the same results as intratumoral injections.
As one of the deadliest diseases, any improvements in cancer treatments can possibly save lives. Since macrophage reprogramming has been a focus of study for many years and generates results that add to the field of oncology, more funding and research needs to be allocated. The substances MPLA and IFNy are already FDA-approved and are used individually in treatments. If further research is completed regarding the mixture of MPLA+IFNy in regards to other types of cancers or cancers in humans, this could become a standard treatment for breast and lung cancer.
 L. Sun, et al., Activating a collaborative innate-adaptive immune response to control metastasis. Cancer cell 39, 1300-1302 (2021). doi: https://doi.org/10.1016/j.ccell.2021.08.005
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