PD-L2在头颈部鳞状细胞癌免疫治疗预后评估中的意义

doi:10.19401/j.cnki.1007-3639.2023.06.009

中国癌症杂志 ›› 2023, Vol. 33 ›› Issue (6): 613-618.doi: 10.19401/j.cnki.1007-3639.2023.06.009

PD-L2在头颈部鳞状细胞癌免疫治疗预后评估中的意义

黄鹤(), 鞠侯雨, 杨文艺, 严明, 任国欣, 胡镜宙()

上海交通大学医学院附属第九人民医院口腔颌面-头颈肿瘤科，上海交通大学口腔医学院，国家口腔医学中心，国家口腔疾病临床医学研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所，上海 200011

收稿日期:2023-03-16 修回日期:2023-06-02 出版日期:2023-06-30 发布日期:2023-07-26
通信作者: 胡镜宙（ORCID：0000-0003-4402-3370），医学博士，主任医师。
作者简介:黄鹤（ORCID：0000-0002-5066-3668），医学学士，硕士研究生在读。

Clinical implication of PD-L2 in the prognosis assessment of HNSCC immunotherapy

HUANG He(), JU Houyu, YANG Wenyi, YAN Ming, REN Guoxin, HU Jingzhou()

Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China

Received:2023-03-16 Revised:2023-06-02 Published:2023-06-30 Online:2023-07-26

摘要/Abstract

摘要：

背景与目的：程序性死亡[蛋白]-1（programmed death-1，PD-1）单抗免疫治疗在头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）中的作用愈发重要，然而目前具有响应率低、缺乏预测性生物标志物的问题。本研究旨在确定程序性死亡[蛋白]配体-2（programmed death ligand-2，PD-L2）能否作为预测HNSCC中PD-1单抗免疫治疗获益情况的生物标志物。方法：收集50例接受PD-1单克隆抗体免疫治疗的中晚期HNSCC的组织标本及临床数据，采用免疫组织化学染色法分析程序性死亡[蛋白]配体-1（programmed death ligand-1，PD-L1）、PD-L2表达量，采用SPSS 26.0软件根据基本临床特征、PD-L1与PD-L2表达量分组统计并进行Kaplan-Meier生存分析，采用GraphPad Prism软件绘制生存曲线。结果：PD-L2在HNSCC患者中阳性表达率较高，有超过80%的患者肿瘤组织可检出PD-L2表达；PD-L2的表达量显著影响免疫治疗结局，PD-L2高表达的患者平均生存期为18.8（16.0 ~ 21.7）个月，而PD-L2低表达的患者平均生存期为11.0（9.1 ~ 12.8）个月，差异有统计学意义（P<0.05）。结论：PD-L2可作为评估HNSCC中PD-1单克隆抗体免疫治疗获益的生物标志物。

关键词: 头颈部鳞状细胞癌, 免疫治疗, PD-L2

Abstract:

Background and purpose: Programmed death-1 (PD-1) monoclonal antibody therapy plays an increasingly important role in the treatment of head and neck squamous cell carcinoma (HNSCC). However, low response rate and lack of predictive biomarkers are still the challenging problems. This study aimed to confirm that programmed death ligand-2 (PD-L2) is a predictive biomarker for the outcome of HNSCC anti-PD-1 immunotherapy. Methods: The samples and clinical data of 50 HNSCC patients undergoing PD-1 monoclonal antibody immunotherapy were collected. Immunohistochemical staining was used to analyze the level of programmed death ligand-1 (PD-L1) and PD-L2. Kaplan-Meier overall survivals were analyzed using SPSS 26.0 software, grouped by the basic clinical characteristics and the PD-L1 and PD-L2 levels. Survival curves were plotted using GraphPad Prism. Results: HNSCC had a relatively high expression rate of PD-L2 with more than 80% of cases detected as PD-L2 positive. The expression of PD-L2 significantly correlated with the clinical outcome of immunotherapy, with a mean survival of 18.8 (16.0-21.7) months for patients with high PD-L2 expression and 11.0 (9.1-12.8) months for patients with low PD-L2 expression, this difference being statistically significant. Conclusion: PD-L2 has the potential to be used as a predictive biomarker for HNSCC anti-PD-1 immunotherapy.

Key words: Head and neck squamous cell carcinoma, Immunotherapy, Programmed death ligand-2

中图分类号:

R739.91

黄鹤, 鞠侯雨, 杨文艺, 严明, 任国欣, 胡镜宙. PD-L2在头颈部鳞状细胞癌免疫治疗预后评估中的意义[J]. 中国癌症杂志, 2023, 33(6): 613-618.

HUANG He, JU Houyu, YANG Wenyi, YAN Ming, REN Guoxin, HU Jingzhou. Clinical implication of PD-L2 in the prognosis assessment of HNSCC immunotherapy[J]. China Oncology, 2023, 33(6): 613-618.

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参考文献 13

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Basic clinical characteristics	Case n (%)
Gender
Male	35 (70.00)
Female	15 (30.00)
Primary site
Oral cavity and mucosal lip	43 (86.00)
Body of tongue	18 (41.86)
Buccal mucosa	9 (20.93)
Lower gingiva	6 (13.95)
Mouth floor	4 (9.30)
Upper gingiva and hard palate	4 (9.30)
Upper lip	1 (2.33)
Lower lip	1 (2.33)
Oropharynx and hypopharynx	6 (12.00)
Parotid gland	1 (2.00)
AJCC staging
Ⅲ	2 (4.00)
Ⅳa	6 (12.00)
Ⅳb	31 (62.00)
Ⅳc	11 (22.00)
Recurrent disease
Yes	47 (94.00)
No	3 (6.00)
Regional lymph node metastasis
Yes	32 (64.00)
No	18 (36.00)
Distal metastasis
Yes	11 (22.00)
No	39 (78.00)

Medical history, laboratory test, and treatment	Case n (%)
Previous history of radiotherapy
Yes	34 (68.00)
No	16 (32.00)
CPS test before treatment
Yes	45 (90.00)
CPS≥1	43 (95.56)
CPS<1	2 (4.44)
No	5 (10.00)
Combined treatment
Combined chemotherapy only	33 (66.00)
Combined target therapy only	11 (22.00)
Combined both chemotherapy and target therapy	3 (6.00)
No combined treatment	3 (6.00)

Characteristics	Case n	Mean OS t/month	P value
Gender			0.234
Male	35	13.03 ± 1.23
Female	15	16.30 ± 1.96
Age/year			0.878
≥58	26	14.35 ± 1.29
<58	24	14.53 ± 1.79
Regional lymph node metastasis			0.336
Yes	32	13.83 ± 1.35
No	18	15.24 ± 1.70
Distal metastasis			0.657
Yes	11	12.22 ± 1.97
No	39	14.84 ± 1.29
Previous history of radiotherapy			0.931
Yes	34	13.88 ± 1.11
No	16	14.32 ± 2.25

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PD-L2在头颈部鳞状细胞癌免疫治疗预后评估中的意义

Clinical implication of PD-L2 in the prognosis assessment of HNSCC immunotherapy

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