홍선미 (아주대학교 의과대학)

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아주대학교 의과대학

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Adv. Sci., Feb 02 2024, | https://doi.org/10.1002/advs.202303177 NAMPT-Driven M2 Polarization of Tumor-Associated Macrophages Leads to an Immunosuppressive Microenvironment in Colorectal Cancer

Sun Mi Hong ^{1 #}, A-Yeon Lee ^{1 2 #}, Byeong-Ju Kim ^{1 2}, Jeong-Eun Lee^{1 2}, Su-Yeon Seon ^{1 2}, Yu-Jin Ha^{1 2}, Jestlin Tianthing Ng ^{1 2}, Gyesoon Yoon ^{1 2}, Su Bin Lim ^{1 2}, Michael J Morgan ³, Jong-Ho Cha^{4 5}, Dakeun Lee ^{2 6}, You-Sun Kim ^{1 2 *}

¹Department of Biochemistry, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea.

²Department of Biomedical Sciences, Graduate School of Ajou University, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea.

³Department of Natural Sciences, Northeastern State University, Tahlequah, OK, 74464, USA.

⁴Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, 22212, South Korea.

⁵Department of Biomedical Science and Engineering, Graduate School, Inha University, Incheon, 22212, South Korea.

⁶Department of Pathology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea.

^#These authors contributed equally
^*Corresponding author: correspondence to You-Sun Kim

Abstract

Nicotinamide phosphoribosyltransferase (NAMPT) is a metabolic enzyme with key roles in inflammation. Previous studies have examined the consequences of its upregulated expression in cancer cells themselves, but studies are limited with respect to its role in the other cells within the tumor microenvironment (TME) during colorectal cancer (CRC) progression. Using single-cell RNA sequencing (scRNA-seq) data, it is founded that NAMPT is highly expressed in SPP1⁺ tumor-associated macrophages (TAMs), a unique subset of TAMs associated with immunosuppressive activity. A NAMPT^high gene signature in SPP1⁺ TAMs correlated with worse prognostic outcomes in CRC patients. The effect of Nampt deletion in the myeloid compartment of mice during CRC development is explored. NAMPT deficiency in macrophages resulted in HIF-1α destabilization, leading to reduction in M2-like TAM polarization. NAMPT deficiency caused significant decreases in the efferocytosis activity of macrophages, which enhanced STING signaling and the induction of type I IFN-response genes. Expression of these genes contributed to anti-tumoral immunity via potentiation of cytotoxic T cell activity in the TME. Overall, these findings suggest that NAMPT-initiated TAM-specific genes can be useful in predicting poor CRC patient outcomes; strategies aimed at targeting NAMPT may provide a promising therapeutic approach for building an immunostimulatory TME in CRC progression.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-06)
연구진국내(교신)+국외 연구진
분야 의약학 > 분자세포의학

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