Vedire Yeshwanth, Seager Robert, Van Roey Erik, Gao Shuang, Nesline Mary, Conroy Jeffrey, Dy Grace, Barbi Joseph, Pabla Sarabjot, Yendamuri Sai
Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
Omniseq, Buffalo, New York, USA, 14263.
Ann Thorac Surg Short Rep. 2023 Sep;1(3):465-468. doi: 10.1016/j.atssr.2023.05.012. Epub 2023 Aug 31.
There exists a gap in understanding the interaction between sex and obesity on tumor microenvironment in NSCLC. We demonstrate the combined effects of sex and body composition on clinically relevant biomarkers of NSCLC immune response.
A cohort of 409 patients with NSCLC was subdivided into 4 groups jointly defined by body mass index (BMI; cutoff of 25 kg/m2) and sex (male-high BMI, male-low BMI, female-high BMI, female-low BMI). Associations between these sex-BMI groups and tumor inflammation (expression of 161 immune response genes), cell proliferation (expression of 10 cell proliferation genes), and programmed cell death ligand 1 (PD-L1; through immunohistochemistry and targeted RNA sequencing) were assessed by Kruskal-Wallis and Wilcoxon rank sum tests for overall and pairwise tests, respectively.
We observed an overall significant association of sex-BMI with tumor inflammation (P < .001) and cell proliferation (P = .002). On pairwise analysis, high-BMI females had significantly higher tumor inflammation compared with low-BMI females (P = .002). In addition, women with a high (P = .004) and low (P = .008) BMI had significantly higher tumor inflammation compared with men with a high and low BMI, respectively. Low-BMI females (P = .01) and males (P = .01) had more cell proliferation. PD-L1 expression by RNA sequencing (P = .001) but not by immunohistochemical analysis differed significantly with sex-BMI. High-BMI females had significantly higher PD-L1 expression compared with low-BMI females (P = .01).
We demonstrate that tumor inflammation and PD-L1 expression are more strongly associated with BMI in women than in men. Additional studies are required to better understand the mechanisms underlying these effects and their role in response to checkpoint inhibitors in NSCLC.
在理解非小细胞肺癌（NSCLC）中性别与肥胖对肿瘤微环境的相互作用方面存在差距。我们展示了性别和身体组成对NSCLC免疫反应的临床相关生物标志物的联合作用。
将409例NSCLC患者队列根据体重指数（BMI；临界值为25kg/m²）和性别（高BMI男性、低BMI男性、高BMI女性、低BMI女性）联合分为4组。通过Kruskal-Wallis检验和Wilcoxon秩和检验分别评估这些性别-BMI组与肿瘤炎症（161个免疫反应基因的表达）、细胞增殖（10个细胞增殖基因的表达）以及程序性细胞死亡配体1（PD-L1；通过免疫组织化学和靶向RNA测序）之间的关联，用于总体检验和两两检验。
我们观察到性别-BMI与肿瘤炎症（P <.001）和细胞增殖（P =.002）总体上存在显著关联。在两两分析中，高BMI女性与低BMI女性相比，肿瘤炎症显著更高（P =.002）。此外，高BMI（P =.004）和低BMI（P =.008）的女性与高BMI和低BMI的男性相比，肿瘤炎症分别显著更高。低BMI女性（P =.01）和男性（P =.01）的细胞增殖更多。通过RNA测序检测的PD-L1表达（P =.001）在不同性别-BMI组间存在显著差异，但免疫组织化学分析未显示出差异。高BMI女性与低BMI女性相比，PD-L1表达显著更高（P =.01）。
我们证明，与男性相比，肿瘤炎症和PD-L1表达在女性中与BMI的关联更强。需要进一步研究以更好地理解这些效应的潜在机制及其在NSCLC中对检查点抑制剂反应的作用。
