Nelson Brad H
Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada.
Immunol Rev. 2008 Apr;222:101-16. doi: 10.1111/j.1600-065X.2008.00614.x.
Ovarian cancer remains a challenging disease for which improved treatments are urgently needed. Most patients present with advanced disease that is highly responsive to surgery combined with platinum- and taxane-based chemotherapy, with a state of minimal residual disease being achieved in many cases. However, chemotherapy-resistant recurrent tumors typically appear within 1-5 years and are ultimately fatal. Recently, several groups have shown that ovarian tumors are often infiltrated by activated T cells at the time of diagnosis, and patients with dense infiltrates of CD3+CD8+ T cells experience unexpectedly favorable progression-free and overall survival. Other cell types in the immune infiltrate oppose anti-tumor immunity, including CD4+CD25+FoxP3+ regulatory T cells, CD8+ regulatory T cells, macrophages, and dendritic cells. The composition of immune infiltrates is shaped by the expression of cytokines, chemokines, antigens, major histocompatibility complex molecules, and costimulatory molecules. The relationship between these various immunological factors is reviewed here with a strong emphasis on outcomes data so as to create a knowledge base that is well grounded in clinical reality. With improved understanding of the functional properties of natural CD8+ T-cell responses to ovarian cancer, there is great potential to improve clinical outcomes by amplifying host immunity.
卵巢癌仍然是一种具有挑战性的疾病,迫切需要改进治疗方法。大多数患者就诊时已处于晚期,对手术联合铂类和紫杉类化疗高度敏感,许多病例可达到微小残留病状态。然而,化疗耐药的复发性肿瘤通常在1 - 5年内出现,最终导致死亡。最近,几个研究小组表明,卵巢肿瘤在诊断时常常被活化的T细胞浸润,CD3 + CD8 + T细胞密集浸润的患者无进展生存期和总生存期出人意料地良好。免疫浸润中的其他细胞类型对抗肿瘤免疫起相反作用,包括CD4 + CD25 + FoxP3 + 调节性T细胞、CD8 + 调节性T细胞、巨噬细胞和树突状细胞。免疫浸润的组成受细胞因子、趋化因子、抗原、主要组织相容性复合体分子和共刺激分子表达的影响。本文综述了这些不同免疫因素之间的关系,并特别强调了结果数据,以便建立一个基于临床实际的知识库。随着对天然CD8 + T细胞对卵巢癌反应功能特性的进一步了解,通过增强宿主免疫力来改善临床结果具有巨大潜力。