Lenehan Patrick J, Cirella Assunta, Uchida Amiko M, Crowley Stephanie J, Sharova Tatyana, Boland Genevieve, Dougan Michael, Dougan Stephanie K, Heckler Max
Department of Cancer Immunology and Virology, Dana Farber Cancer Institute, Boston, MA, USA.
Department of Immunology, Harvard Medical School, Boston, MA, USA.
Immunother Adv. 2021 Jun 2;1(1):ltab011. doi: 10.1093/immadv/ltab011. eCollection 2021 Jan.
Cachexia is a systemic metabolic disorder characterized by loss of fat and muscle mass, which disproportionately impacts patients with gastrointestinal malignancies such as pancreatic cancer. While the immunologic shifts contributing to the development of other adipose tissue (AT) pathologies such as obesity have been well described, the immune microenvironment has not been studied in the context of cachexia.
We performed bulk RNA-sequencing, cytokine arrays, and flow cytometry to characterize the immune landscape of visceral AT (VAT) in the setting of pancreatic and colorectal cancers.
The cachexia inducing factor IL-6 is strongly elevated in the wasting VAT of cancer bearing mice, but the regulatory type 2 immune landscape which characterizes healthy VAT is maintained. Pathologic skewing toward Th1 and Th17 inflammation is absent. Similarly, the VAT of patients with colorectal cancer is characterized by a Th2 signature with abundant IL-33 and eotaxin-2, albeit also with high levels of IL-6.
Wasting AT during the development of cachexia may not undergo drastic changes in immune composition like those seen in obese AT. Our approach provides a framework for future immunologic analyses of cancer associated cachexia.
恶病质是一种全身性代谢紊乱，其特征是脂肪和肌肉量减少，对胰腺癌等胃肠道恶性肿瘤患者的影响尤为严重。虽然导致肥胖等其他脂肪组织（AT）病变发展的免疫变化已得到充分描述，但尚未在恶病质背景下研究免疫微环境。
我们进行了批量RNA测序、细胞因子阵列分析和流式细胞术，以表征胰腺癌和结直肠癌背景下内脏AT（VAT）的免疫格局。
恶病质诱导因子IL-6在荷癌小鼠消瘦的VAT中显著升高，但表征健康VAT的调节性2型免疫格局得以维持。不存在向Th1和Th17炎症的病理性偏向。同样，结直肠癌患者的VAT以具有丰富IL-33和嗜酸性粒细胞趋化因子-2的Th2特征为特点，尽管IL-6水平也很高。
恶病质发展过程中消瘦的AT可能不会像肥胖AT那样在免疫组成上发生剧烈变化。我们的方法为未来癌症相关恶病质的免疫分析提供了一个框架。
