The top journal Qi Qiwen: Macrophages become cancer immunotherapy

Macrophages, as an important part of innate immunity, usually act as "leaders" against pathogen invasion and "communicators" that activate adaptive immunity. However, in the tumor environment, it can not help the "temptation" of some signal molecules released by tumor cells, and become a "rebel": it not only prevents T cells from attacking tumor cells, but also secretes growth factors to nourish tumor cells and promote The formation of tumor blood vessels leads to the spread of tumor cells. According to statistics, macrophages can account for half of the total weight of the tumor! In the face of so many "defective" macrophages, is there any way to change the tumor environment, "re-educating" macrophages, making them "washed" and re-emerging anti-cancer effects?

Recently, the results of two female scientists have given the answer: Jennifer Guerriero uses an enzyme inhibitor, Sharareh Gholamin, to use an antibody, and to re-educate macrophages, so that they can play an anti-cancer role again. In the mouse model, tumor growth slows or subsides and no longer metastasizes! Their research results were published in Nature and Science Translational Medicine.

顶级期刊齐发文:巨噬细胞成为癌症免疫治疗悍将

Left is Jennifer Guerriero, right is Sharareh Gholamin

Guerriero, from the Dana Farber Cancer Center, and other researchers used an enzyme inhibitor called TMP195 to "make the macrophage" back into the mouse model of breast cancer, shrinking the mass and preventing lung metastasis. When TMP195 is used in combination with a chemotherapeutic drug or its PD-1 inhibitor, the corresponding efficacy and tolerability are improved.

As early as 2013, the researchers found that TMP195 can in vitro, let macrophages "wash the heart", from "rebels" that promote tumor growth to "undercover" to attack tumor tissue [5]. TMP195 is an inhibitor of class IIa histone deacetylase (Class IIa HDAC). In the tumor environment, tumor cells regulate the proliferation and differentiation of macrophages by means of class IIa HDACs. Usually, this enzyme will cause macrophages to embark on a "dangerous path" that is conducive to the growth of tumor cells. When TMP195 binds to this enzyme, it blocks the "misleading" pathway of tumor cells, causing macrophages to "reform the evils and correct them" and embark on the correct path of tumor suppression.

In light of previous research, Guerriero and his team suspected that TMP195 also "re-educates" macrophages in vivo, inducing an anti-tumor innate immune response to regress the tumor. They selected a mouse model that mimics breast cancer, in which advanced canceration and lung metastasis are controlled by macrophages.

The researchers first injected mice with TMP195 for five consecutive days to see if macrophages in mouse tumors could be "re-educated" by TMP195. They found that a series of immune responses did occur in the tumor site of the mouse: the number of cancer-promoting macrophages was reduced, while new tumor suppressor macrophages increased and activated T cells that killed cancer cells. In addition, TMP195 also reduces abnormal branching of blood vessels in tumors, increases tumor apoptosis, and reduces tumor proliferation! This shows that the macrophages in the tumor are not "stubborn", and after "re-education", they will still "get lost."

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