CALGB/SWOG 80405 是一项随机 III 期试验，在一线接受贝伐单抗、西妥昔单抗或两者联合化疗的转移性结直肠癌患者中进行。我们测试了肿瘤免疫特征对总生存期 (OS) 的影响

通过 RNA 测序对原发性肿瘤 (N = 554) 进行了分析。测量了巨噬细胞、淋巴细胞、TGFβ、IFNγ、伤口愈合和细胞毒性的免疫特征。测量了幼稚和记忆 B 细胞、浆细胞、CD8+ T 细胞、静息和活化记忆 CD4+ T 细胞、M0 和 M2 巨噬细胞以及活化肥大细胞的 CIBERSORTx 评分。

M2 巨噬细胞评分增加 [HR，6.30； 95% 置信区间 (CI), 3.0-12.15] 和 TGFβ 特征表达 (HR, 1.35; 95% CI, 1.05-1.77) 与较短的 OS 相关。浆细胞（HR，0.55；95% CI，0.38-0.87）和活化记忆 CD4+ T 细胞（HR，0.34；95% CI，0.16-0.65）得分增加与更长的 OS 相关。使用这四个特征的最佳截止值，患者被归类为具有与较长 OS 相关的 4、3、2 或 0-1 个有益特征，中位 (95% CI) OS 从 42.5 (35.8-47.8) 下降到 31.0 (28.8-34.4)、25.2 (20.6-27.9) 和 17.7 (13.5-20.4) 个月 (P = 3.48e-11)。可以进一步评估新的免疫功能以改善患者的反应。它们为更有效的免疫治疗策略提供了依据。

Abstract

Purpose: CALGB/SWOG 80405 was a randomized phase III trial in first-line patients with metastatic colorectal cancer treated with bevacizumab, cetuximab, or both, plus chemotherapy. We tested the effect of tumor immune features on overall survival (OS).

Experimental design: Primary tumors (N = 554) were profiled by RNA sequencing. Immune signatures of macrophages, lymphocytes, TGFβ, IFNγ, wound healing, and cytotoxicity were measured. CIBERSORTx scores of naive and memory B cells, plasma cells, CD8+ T cells, resting and activated memory CD4+ T cells, M0 and M2 macrophages, and activated mast cells were measured.

Results: Increased M2 macrophage score [HR, 6.30; 95% confidence interval (CI), 3.0-12.15] and TGFβ signature expression (HR, 1.35; 95% CI, 1.05-1.77) were associated with shorter OS. Increased scores of plasma cells (HR, 0.55; 95% CI, 0.38-0.87) and activated memory CD4+ T cells (HR, 0.34; 95% CI, 0.16-0.65) were associated with longer OS. Using optimal cutoffs from these four features, patients were categorized as having either 4, 3, 2, or 0-1 beneficial features associated with longer OS, and the median (95% CI) OS decreased from 42.5 (35.8-47.8) to 31.0 (28.8-34.4), 25.2 (20.6-27.9), and 17.7 (13.5-20.4) months respectively (P = 3.48e-11).

Conclusions: New immune features can be further evaluated to improve patient response. They provide the rationale for more effective immunotherapy strategies.

原文链接

pubmed.ncbi.nlm.nih.gov/35176136/

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