ELIZA

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14) Further, leptin and anti-PD-1 cotreatment may enhance antitumor effects consistent with an increase in M1-like tumor-associated macrophage frequency compared with non-leptin-treated mice.

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PMID:34772698 DOI:10.4049/jimmunol.2001152

2021 Journal of immunology (Baltimore, Md. : 1950)

* Leptin Augments Antitumor Immunity in Obesity by Repolarizing Tumor-Associated Macrophages.

- Although obesity can promote cancer, it may also increase immunotherapy efficacy in what has been termed the obesity-immunotherapy paradox. Mechanisms of this effect are unclear, although obesity alters key inflammatory cytokines and can promote an inflammatory state that may modify tumor-infiltrating lymphocytes and tumor-associated macrophage populations. To identify mechanisms by which obesity affects antitumor immunity, we examined changes in cell populations and the role of the proinflammatory adipokine leptin in immunotherapy. Single-cell RNAseq demonstrated that obesity decreased tumor-infiltrating lymphocyte frequencies, and flow cytometry confirmed altered macrophage phenotypes with lower expression of inducible NO synthase and MHC class II in tumors of obese animals. When treated with anti-programmed cell death protein 1 (PD-1) Abs, however, obese mice had a greater absolute decrease in tumor burden than lean mice and a repolarization of the macrophages to inflammatory M1-like phenotypes. Mechanistically, leptin is a proinflammatory adipokine that is induced in obesity and may mediate enhanced antitumor immunity in obesity. To directly test the effect of leptin on tumor growth and antitumor immunity, we treated lean mice with leptin and observed tumors over time. Treatment with leptin, acute or chronic, was sufficient to enhance antitumor efficacy similar to anti-PD-1 checkpoint therapy. Further, leptin and anti-PD-1 cotreatment may enhance antitumor effects consistent with an increase in M1-like tumor-associated macrophage frequency compared with non-leptin-treated mice. These data demonstrate that obesity has dual effects in cancer through promotion of tumor growth while simultaneously enhancing antitumor immunity through leptin-mediated macrophage reprogramming.

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--- WordNet output for increase --- =>大きくなる, を増す, 増大させる, 強まる, 増加, 増える, 増やす Overview of noun increase The noun increase has 5 senses (first 5 from tagged texts) 1. (49) addition, increase, gain -- (a quantity that is added; "there was an addition to property taxes this year"; "they recorded the cattle's gain in weight over a period of weeks") 2. (21) increase -- (a change resulting in an increase; "the increase is scheduled for next month") 3. (7) increase, increment, growth -- (a process of becoming larger or longer or more numerous or more important; "the increase in unemployment"; "the growth of population") 4. (3) increase, increment -- (the amount by which something increases; "they proposed an increase of 15 percent in the fare") 5. (3) increase, step-up -- (the act of increasing something; "he gave me an increase in salary") Overview of verb increase The verb increase has 2 senses (first 2 from tagged texts) 1. (86) increase -- (become bigger or greater in amount; "The amount of work increased") 2. (61) increase -- (make bigger or more; "The boss finally increased her salary"; "The university increased the number of students it admitted") --- WordNet end ---