由于只有一部分癌症患者可以从免疫治疗中受益，因此识别 ICI 治疗反应的预测生物标志物至关重要。我们分析了 1,479 名接受 ICI 治疗的 16 种癌症患者的血红蛋白 (HGB) 水平与临床结果之间的关联。我们使用基于样条的 cox 回归分析探讨了 HGB 水平与生存和免疫治疗反应之间的剂量依赖性关联。此外，我们使用引导重采样方法调查了具有不同临床病理特征、治疗方案和癌症类型的患者亚组之间的关联。在接受免疫治疗的癌症患者中，HGB 水平与临床结果呈正相关，但在未接受免疫治疗的癌症患者中则不然。此外，这种关联独立于其他临床病理特征（如性别、年龄、肿瘤分期和肿瘤突变负荷（TMB））、治疗方案和癌症类型。此外，这种关联独立于免疫治疗反应的既定生物标志物，包括 TMB、PD-L1 表达和微卫星不稳定性。 TMB 和 HGB 水平的组合在预测免疫治疗反应方面比单独使用 TMB 更有效。多组学分析表明，HGB 水平与抗肿瘤免疫特征呈正相关，与指导抗肿瘤免疫抑制的肿瘤特性（如同源重组缺陷、干性和肿瘤内异质性）呈负相关。HGB 测量作为免疫治疗反应的新型生物标志物具有潜在的临床价值。通过临床常规检查很容易获得。 TMB 和 HGB 测量的组合比 TMB 具有更好的免疫治疗反应预测性能。版权所有 © 2024 He、Ren、Ji、Zhao 和 Wang。

Because only a subset of cancer patients can benefit from immunotherapy, identifying predictive biomarkers of ICI therapy response is of utmost importance.We analyzed the association between hemoglobin (HGB) levels and clinical outcomes in 1,479 ICIs-treated patients across 16 cancer types. We explored the dose-dependent associations between HGB levels and survival and immunotherapy response using the spline-based cox regression analysis. Furthermore, we investigated the associations across subgroups of patients with different clinicopathological characteristics, treatment programs and cancer types using the bootstrap resampling method.HGB levels correlated positively with clinical outcomes in cancer patients receiving immunotherapy but not in those without immunotherapy. Moreover, this association was independent of other clinicopathological characteristics (such as sex, age, tumor stage and tumor mutation burden (TMB)), treatment program and cancer type. Also, this association was independent of the established biomarkers of immunotherapy response, including TMB, PD-L1 expression and microsatellite instability. The combination of TMB and HGB level are more powerful in predicting immunotherapy response than TMB alone. Multi-omics analysis showed that HGB levels correlated positively with antitumor immune signatures and negatively with tumor properties directing antitumor immunosuppression, such as homologous recombination defect, stemness and intratumor heterogeneity.The HGB measure has the potential clinical value as a novel biomarker of immunotherapy response that is easily accessible from clinically routine examination. The combination of TMB and HGB measures have better predictive performance for immunotherapy response than TMB.Copyright © 2024 He, Ren, Ji, Zhao and Wang.