癌症患者接受免疫检查点抑制剂治疗时流感疫苗的细胞介导免疫原性。

Cell-Mediated Immunogenicity of Influenza Vaccination in Patients With Cancer Receiving Immune Checkpoint Inhibitors.

机构信息

Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

Department of Anatomy and Cell Biology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.

出版信息

J Infect Dis. 2020 Nov 9;222(11):1902-1909. doi: 10.1093/infdis/jiaa291.

DOI:10.1093/infdis/jiaa291

PMID:32479600

Abstract

BACKGROUND

We assessed cell-mediated immune (CMI) responses of influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs), which remain elusive.

METHODS

Vaccine-elicited CMI responses in patients receiving ICIs or cytotoxic agents were investigated by flow cytometry. Polyfunctional cells were defined as T cells that express 2 or more of interleukin 2 (IL-2), interleukin 4 (IL-4), interferon gamma (IFN-γ), and CD107a. An adequate CMI response was defined as an increase of polyfunctional T cells against both H1N1 and H3N2 strains.

RESULTS

When comparing ICI (n = 11) and cytotoxic chemotherapy (n = 29) groups, H1N1-specific IL-4 or IFN-γ-expressing CD4+ T cells, IL-2, IL-4, IFN-γ, or CD107a-expressing CD8+ T cells, H3N2-specific IFN-γ-expressing CD4+ T cells, and CD107a-expressing CD8+ T cells were more frequent in the ICI group. Fold changes in polyfunctional H3N2-specific CD4+ (median, 156.0 vs 95.7; P = .005) and CD8+ (155.0 vs 103.4; P = .044) T cells were greater in the ICI group. ICI administration was strongly associated with an adequate CMI response for both CD4+ and CD8+ T cells (P = .003).

CONCLUSIONS

CMI responses following influenza vaccination were stronger in the ICI group than in the cytotoxic chemotherapy group. Influenza vaccination should be strongly recommended in patients with cancer receiving ICIs.

摘要

背景

我们评估了接受免疫检查点抑制剂（ICI）治疗的癌症患者的流感疫苗接种引起的细胞介导免疫（CMI）反应，但结果仍不清楚。

方法

通过流式细胞术研究接受 ICI 或细胞毒性药物治疗的患者的疫苗引起的 CMI 反应。多功能细胞定义为表达 2 种或更多白细胞介素 2（IL-2）、白细胞介素 4（IL-4）、干扰素 γ（IFN-γ）和 CD107a 的 T 细胞。足够的 CMI 反应定义为针对 H1N1 和 H3N2 株的多功能 T 细胞增加。

结果

在比较 ICI（n=11）和细胞毒性化疗（n=29）组时，ICI 组中 H1N1 特异性 IL-4 或 IFN-γ 表达的 CD4+T 细胞、IL-2、IL-4、IFN-γ 或 CD107a 表达的 CD8+T 细胞、H3N2 特异性 IFN-γ 表达的 CD4+T 细胞和 CD107a 表达的 CD8+T 细胞更为频繁。多功能 H3N2 特异性 CD4+（中位数，156.0 比 95.7；P=0.005）和 CD8+（155.0 比 103.4；P=0.044）T 细胞的倍数变化在 ICI 组中更大。ICI 给药与 CD4+和 CD8+T 细胞的足够 CMI 反应强烈相关（P=0.003）。