Pan-immune-inflammation value predicts immunotherapy response and reflects local antitumor immune response in rectal cancer.

IF 5.7 2区 医学 Q1 Medicine
Cancer Science Pub Date : 2024-11-27 DOI:10.1111/cas.16400
Qianyu Wang, Wentao Zhong, Yi Xiao, Guole Lin, Junyang Lu, Lai Xu, Guannan Zhang, Aijun Liu, Junfeng Du, Bin Wu
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引用次数: 0

Abstract

The pan-immune-inflammation value reflects the systemic inflammatory response, and tumor-infiltrating lymphocytes indicate a local immune response in rectal cancer. However, the association between systemic inflammatory response, as indicated by the pan-immune-inflammation value, and local immune responses in rectal cancer remains unclear. This study analyzed 915 treatment-naïve rectal cancer patients from the Peking Union Medical College Hospital and PLA General Hospital (PLAGH) cohorts who underwent radical surgery to investigate the relationship between the pan-immune-inflammation value and immune responses. Lower pan-immune-inflammation value was significantly associated with improved disease-free survival and cancer-specific survival. Multivariate Cox regression models identified the pan-immune-inflammation value as an independent prognostic factor. In the PLAGH cohort, patients with low pan-immune-inflammation values had higher immune cell levels, activated immune pathways, and increased expression of immune checkpoint genes according to RNA sequencing. Hematoxylin and eosin staining and immunohistochemical analysis revealed that lower pan-immune-inflammation value was associated with higher tumor-infiltrating lymphocyte density, more mature tertiary lymphoid structures, increased CD8+ T cells, and elevated human lymphocyte antigen class I expression. Conversely, patients with high pan-immune-inflammation values exhibited pathways linked to tumor progression, such as angiogenesis, epithelial-mesenchymal transition, hypoxia, KRAS signaling, and TGF-ß signaling. Among patients receiving anti-PD-1 therapy, responders had low pre- and post-treatment pan-immune-inflammation values. The pan-immune-inflammation value is a reliable marker associated with distinct immune microenvironment characteristics and can effectively predict disease-free survival, cancer-specific survival, and response to immunotherapy.

泛免疫炎症值可预测免疫疗法反应并反映直肠癌的局部抗肿瘤免疫反应。
泛免疫炎症值反映了全身炎症反应,而肿瘤浸润淋巴细胞则表明直肠癌的局部免疫反应。然而,泛免疫炎症值所显示的全身炎症反应与直肠癌局部免疫反应之间的关系仍不清楚。本研究分析了北京协和医院和中国人民解放军总医院(PLAGH)队列中接受根治性手术的 915 例未经治疗的直肠癌患者,以探讨泛免疫炎症值与免疫反应之间的关系。泛免疫炎症值越低,无病生存率和癌症特异性生存率越高。多变量考克斯回归模型确定泛免疫炎症值是一个独立的预后因素。在PLAGH队列中,根据RNA测序,泛免疫炎症值较低的患者免疫细胞水平较高,免疫通路被激活,免疫检查点基因表达增加。血色素和伊红染色及免疫组化分析表明,泛免疫炎症值较低的患者肿瘤浸润淋巴细胞密度较高、三级淋巴结构更成熟、CD8+ T细胞增多、人类淋巴细胞抗原I类表达升高。相反,泛免疫炎症值高的患者表现出与肿瘤进展相关的通路,如血管生成、上皮-间质转化、缺氧、KRAS 信号转导和 TGF-ß 信号转导。在接受抗PD-1治疗的患者中,应答者在治疗前和治疗后的泛免疫炎症值较低。泛免疫炎症值是与独特的免疫微环境特征相关的可靠标志物,能有效预测无病生存期、癌症特异性生存期和对免疫疗法的反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cancer Science
Cancer Science ONCOLOGY-
CiteScore
9.90
自引率
3.50%
发文量
406
审稿时长
17 weeks
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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