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癌症患者抵御新病原体的淋巴细胞亚群。

Lymphocyte Subsets in Defense Against New Pathogens in Patients with Cancer.

机构信息

Immunology Laboratory, National Oncology and Radiobiology Institute (INOR), Havana, Cuba.

Havana Medical University, Havana, Cuba.

出版信息

MEDICC Rev. 2022 May 16;24(2):26-34. doi: 10.37757/mr2022.v24.n2.5.

DOI:10.37757/mr2022.v24.n2.5
PMID:35648060
Abstract

INTRODUCTION

Immunity in cancer patients is modified both by the cancer itself and by oncospecific treatments. Whether a patient's adaptive immunity is impaired depends on their levels of naive lymphocytes and other cell populations. During the COVID-19 pandemic, cancer patients are at greater risk of progressing to severe forms of the disease and have higher mortality rates than individuals without cancer, particularly while they are receiving cancer-specific therapies. An individual's protection against infection, their response to vaccines, and even the tests that determine the humoral immune response to SARS-CoV-2, depend on lymphocyte populations, meriting their study.

OBJECTIVE

Estimate blood concentrations of lymphocytes involved in the immune response to new pathogens in cancer patients.

METHODS

We carried out an analytical study of 218 cancer patients; 124 women and 94 men, 26-93 years of age, who were treated at the National Oncology and Radiobiology Institute in Havana, Cuba, March-June, 2020. Patients were divided into five groups: (1) those with controlled disease who were not undergoing cancer-specific treatment; (2) those undergoing debulking surgery; (3) patients undergoing chemotherapy; (4) patients undergoing radiation therapy and (5) patients currently battling infection. We evaluated the following peripheral blood lymphocyte subpopulations via flow cytometry: B lymphocytes (total, naive, transitional, memory, plasmablasts and plasma cells); T lymphocytes (total, helper, cytotoxic and their respective naive, activated, central memory and effector memory subsets); and total, secretory and cytotoxic natural killer cells and T natural killer cells. We also estimated neutrophil/lymphocyte ratios. Lymphocyte concentrations were associated with controlled disease and standard cancer therapy. For variables that did not fall within a normal distribution, ranges were set by medians and 2.5-97.5 percentiles. The two-tailed Mann-Whitney U test was used to measure the effect of sex and to compare lymphocyte populations. We calculated odds ratios to estimate lymphopenia risk.

RESULTS

All cancer patients had lower values of naive helper and cytotoxic T lymphocyte populations, naive B lymphocytes, and natural killer cells than normal reference medians. Naive helper T cells were the most affected subpopulation. Memory B cells, plasmablasts, plasma cells, activated T helper cells, and cytotoxic central memory T cells were increased. Patients undergoing treatment had lower levels of naive lymphocytes than untreated patients, particularly during radiation therapy. The risk of B lymphopenia was higher in patients in treatment. The odds ratio for B lymphopenia was 8.0 in patients who underwent surgery, 12.9 in those undergoing chemotherapy, and 13.9 in patients in radiotherapy.

CONCLUSIONS

Cancer and conventional cancer therapies significantly affect peripheral blood B lymphocyte levels, particularly transitional T helper lymphocytes, reducing the immune system's ability to trigger primary immune responses against new antigens.

摘要

简介

癌症患者的免疫功能既受癌症本身影响,也受肿瘤特异性治疗影响。患者的适应性免疫是否受损取决于其初始淋巴细胞和其他细胞群体的水平。在 COVID-19 大流行期间,癌症患者进展为疾病严重形式的风险更高,死亡率高于无癌症患者,尤其是在接受癌症特异性治疗时。个体对感染的保护、对疫苗的反应,甚至用于确定针对 SARS-CoV-2 的体液免疫反应的检测,都依赖于淋巴细胞群体,值得对其进行研究。

目的

评估癌症患者中参与新病原体免疫反应的淋巴细胞的血液浓度。

方法

我们对 218 名癌症患者进行了一项分析性研究;其中 124 名女性,94 名男性,年龄 26-93 岁,均于 2020 年 3 月至 6 月在古巴哈瓦那国家肿瘤学和放射生物学研究所接受治疗。患者分为五组:(1)疾病控制组,未接受癌症特异性治疗;(2)接受减瘤手术的患者;(3)接受化疗的患者;(4)接受放疗的患者和(5)目前正在感染的患者。我们通过流式细胞术评估了以下外周血淋巴细胞亚群:B 淋巴细胞(总、初始、过渡、记忆、浆母细胞和浆细胞);T 淋巴细胞(总、辅助、细胞毒性及其各自的初始、激活、中央记忆和效应记忆亚群);总、分泌和细胞毒性自然杀伤细胞和 T 自然杀伤细胞。我们还估计了中性粒细胞/淋巴细胞比值。淋巴细胞浓度与疾病控制和标准癌症治疗相关。对于不符合正态分布的变量,范围通过中位数和 2.5-97.5 百分位数确定。使用双尾曼-惠特尼 U 检验测量性别效应并比较淋巴细胞群体。我们计算了比值比以估计淋巴细胞减少症的风险。

结果

所有癌症患者的初始辅助和细胞毒性 T 淋巴细胞、初始 B 淋巴细胞和自然杀伤细胞的数值均低于正常参考中位数。初始辅助 T 细胞是受影响最严重的亚群。记忆 B 细胞、浆母细胞、浆细胞、激活的辅助 T 细胞和细胞毒性中央记忆 T 细胞增加。接受治疗的患者的初始淋巴细胞水平低于未接受治疗的患者,尤其是在接受放疗时。治疗患者发生 B 淋巴细胞减少症的风险更高。接受手术的患者 B 淋巴细胞减少症的比值比为 8.0,接受化疗的患者为 12.9,接受放疗的患者为 13.9。

结论

癌症和常规癌症治疗显著影响外周血 B 淋巴细胞水平,尤其是过渡性辅助 T 淋巴细胞,降低了免疫系统触发针对新抗原的初次免疫反应的能力。

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