Iwase Toshiaki, Parikh Aaroh, Wenli Dong, Shen Yu, Adams Daniel L, Tang Cha-Mei, Cohen Evan N, Reuben James M, Shrimanker Tushaar Vishal, Chainitikun Sudpreeda, Kida Kumiko, Raghavendra Akshara Singareeka, Sapon Maryanne E, Sahin Onur, James Anjali, Sridhar Nithya, Klopp Ann H, Tripathy Debasish, Ueno Naoto T
Section of Translational Breast Cancer Research, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
University of Hawai'i Cancer Center, 701 Ilalo Street Honolulu, HI 96813, USA.
J Cancer. 2024 Sep 16;15(18):5855-5862. doi: 10.7150/jca.89453. eCollection 2024.
Cancer-associated macrophage-like cells (CAMLs) are rare, gigantic, and atypical circulating cells found exclusively in the peripheral blood of patients with solid cancers. Obesity-induced hypoxia attracts macrophages to the tumor microenvironment, where they contribute to establishing chronic inflammation, leading to cancer progression. We hypothesized that obese patients with advanced breast cancer may have CAML profiles different from those of nonobese patients, and these profiles may correlate with proinflammatory markers or other macrophage-related markers. We prospectively collected 20 mL of peripheral blood from patients diagnosed with stage 2-4 breast cancer. We identified CAMLs using the CellSieve microfiltration system and in parallel quantified the proinflammatory and macrophage-related markers using a multiplex cytokine panel. We further evaluated C-X-C chemokine receptor type 4 (CXCR4) expression in CAMLs to investigate its relationship to the macrophage differentiation. We estimated the association between CAML characteristics and body mass index (BMI), body composition, and cytokines/chemokines. Thirty patients were included in the study, and 28 samples were analyzed. Higher BMI was significantly correlated with the increased maximum CAML size ( = 0.035). Patients with higher BMIs had significantly increased macrophage-colony stimulating factor (M-CSF) levels in plasma ( = 0.007), and obese patients trended towards higher tumor necrosis factor-alpha, MIP-1α and M-CSF expression ( <0.10). Body composition analysis showed that the M-CSF and SAT amounts were significantly correlated ( = 0.010). MIP-1α expression was significantly correlated with average CXCR4 CAML expression ( = 0.003). We discovered larger CAML size was associated with SAT-dominant obesity with increased macrophage-related and proinflammatory markers in obese than in nonobese breast cancer patients.
癌症相关巨噬细胞样细胞（CAMLs）是一种罕见、巨大且非典型的循环细胞，仅在实体癌患者的外周血中发现。肥胖诱导的缺氧吸引巨噬细胞至肿瘤微环境，在那里它们促进慢性炎症的形成，从而导致癌症进展。我们推测，晚期乳腺癌肥胖患者的CAML特征可能与非肥胖患者不同，且这些特征可能与促炎标志物或其他巨噬细胞相关标志物相关。我们前瞻性地收集了20毫升被诊断为2 - 4期乳腺癌患者的外周血。我们使用细胞筛微滤系统鉴定CAMLs，并同时使用多重细胞因子检测板对促炎和巨噬细胞相关标志物进行定量。我们进一步评估了CAMLs中C - X - C趋化因子受体4（CXCR4）的表达，以研究其与巨噬细胞分化的关系。我们估计了CAML特征与体重指数（BMI）、身体组成以及细胞因子/趋化因子之间的关联。该研究纳入了30名患者，对28份样本进行了分析。较高的BMI与CAML最大尺寸增加显著相关（P = 0.035）。BMI较高的患者血浆中巨噬细胞集落刺激因子（M - CSF）水平显著升高（P = 0.007），肥胖患者的肿瘤坏死因子 - α、MIP - 1α和M - CSF表达有升高趋势（P < 0.10）。身体组成分析表明，M - CSF与皮下脂肪量显著相关（P = 0.010）。MIP - 1α表达与CAML平均CXCR4表达显著相关（P = 0.003）。我们发现，与非肥胖乳腺癌患者相比，较大的CAML尺寸与以皮下脂肪为主的肥胖相关，肥胖患者中巨噬细胞相关和促炎标志物增加。
