HIV相关弥漫性大B细胞淋巴瘤中的基质免疫浸润与HIV疾病史及患者生存率相关。
Stromal immune infiltration in HIV-related diffuse large B-cell lymphoma is associated with HIV disease history and patient survival.
作者信息
Chao Chun, Xu Lanfang, Silverberg Michael J, Martínez-Maza Otoniel, Chen Lie-Hong, Castor Brandon, Abrams Donald I, Zha Hongbin D, Haque Reina, Said Jonathan
机构信息
aDepartment of Research and Evaluation, Kaiser Permanente Southern California, Pasadena bDivision of Research, Kaiser Permanente Northern California, Oakland cDepartments of Obstetrics and Gynecology and Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles dDepartment of Epidemiology, UCLA Fielding School of Public Health, Los Angeles eDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles fDepartment of Medicine and San Francisco General Hospital, University of California, San Francisco, San Francisco gLos Angeles Medical Center, Kaiser Permanente Southern California, Los Angeles, California, USA.
出版信息
AIDS. 2015 Sep 24;29(15):1943-51. doi: 10.1097/QAD.0000000000000780.
OBJECTIVE
Understanding tumor microenvironment and its impact on prognosis of HIV-related lymphomas may provide insight into novel therapeutic strategies.
DESIGN
We characterized the relationship between infiltrating immune cells with tumor characteristics, HIV disease history and survival in 80 patients with HIV-related diffuse large B-cell lymphoma (DLBCL) diagnosed in the era of combined antiretroviral therapy (1996-2007) at Kaiser Permanente California. Eighty patients with HIV-unrelated DLBCL were included for comparison.
METHODS
Data on patients' clinical history were obtained from Kaiser Permanente's electronic health records. The density of stromal CD4, CD8 and FOXP3 T cells and CD68 macrophages, as well as tumor molecular characteristics were examined using immunohistochemistry. The associations between stromal immune infiltration and patient's clinical history or tumor characteristics were examined using Kruskal-Wallis tests or Pearson's correlation coefficient. The effect of stromal immune infiltration on 2-year mortality was evaluated in multivariable logistic regression.
RESULTS
Compared with HIV-unrelated DLBCL, patients with HIV-related DLBCL had significantly reduced stromal CD4 and FOXP3 T cells, but increased density of macrophages. Increased density of stromal macrophages was correlated with lower circulating CD4 cell count at DLBCL diagnosis. Tumor molecular characteristics, including BCL6, p53 and cMYC expression, but not Epstein-Barr virus infection status, were significantly correlated with stromal immune infiltration, particularly FOXP3 T cells. A higher density of infiltrating CD8 T cell was significantly associated with reduced mortality in patients with HIV-related DLBCL (odds ratio = 0.30 [0.09-0.97] for ≥25 vs. <10%).
CONCLUSION
These data provide evidence for the prognostic significance of cytotoxic T cells in determining outcomes of HIV-related lymphoma.
目的
了解肿瘤微环境及其对HIV相关淋巴瘤预后的影响，可能为新的治疗策略提供思路。
设计
我们对加利福尼亚州凯撒医疗机构在联合抗逆转录病毒治疗时代（1996 - 2007年）诊断的80例HIV相关弥漫性大B细胞淋巴瘤（DLBCL）患者中浸润性免疫细胞与肿瘤特征、HIV疾病史及生存情况之间的关系进行了特征分析。纳入80例非HIV相关DLBCL患者作为对照。
方法
从凯撒医疗机构的电子健康记录中获取患者临床病史数据。采用免疫组织化学法检测基质CD4、CD8和FOXP3 T细胞以及CD68巨噬细胞的密度，以及肿瘤分子特征。使用Kruskal - Wallis检验或Pearson相关系数检验基质免疫浸润与患者临床病史或肿瘤特征之间的关联。在多变量逻辑回归中评估基质免疫浸润对2年死亡率的影响。
结果
与非HIV相关DLBCL相比，HIV相关DLBCL患者的基质CD4和FOXP3 T细胞显著减少，但巨噬细胞密度增加。基质巨噬细胞密度增加与DLBCL诊断时较低的循环CD4细胞计数相关。肿瘤分子特征，包括BCL6、p53和cMYC表达，但不包括爱泼斯坦 - 巴尔病毒感染状态，与基质免疫浸润显著相关，尤其是FOXP3 T细胞。浸润性CD8 T细胞密度较高与HIV相关DLBCL患者死亡率降低显著相关（≥25% vs. <10%时的比值比 = 0.30 [0.09 - 0.97]）。
结论
这些数据为细胞毒性T细胞在确定HIV相关淋巴瘤预后中的预后意义提供了证据。
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