Medical Oncology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Molecular Virology Unit, Department of Microbiology and Virology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
ESMO Open. 2022 Feb;7(1):100359. doi: 10.1016/j.esmoop.2021.100359. Epub 2021 Dec 11.
The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine.
In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/10 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy.
The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/10 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively).
Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors.
SARS-CoV-2 疫苗接种在癌症患者中的免疫原性持久性仍有待阐明。我们前瞻性评估了 BNT162b2 疫苗接种 6 个月后，在接受抗程序性细胞死亡蛋白 1/程序性死亡配体 1 治疗的癌症患者中，疫苗在引发体液和细胞介导免疫反应方面的免疫原性，这些患者或接受化疗，或未接受化疗。
在之前的研究中，共纳入 88 例患者，而以下分析仅针对随访时仍在接受免疫治疗的 60 例患者。根据之前对 SARS-CoV-2 的接触情况，患者被分为 SARS-CoV-2 初治（无 SARS-CoV-2 既往暴露）和 SARS-CoV-2 既往感染（有 SARS-CoV-2 既往感染）。定量检测血清样本中针对 B.1.1 株的中和抗体（NT Ab）滴度和总抗刺突免疫球蛋白 G 浓度。酶联免疫斑点法用于定量检测抗刺突干扰素-γ（IFN-γ）产生细胞/10 个外周血单个核细胞。50 例（83.0%）患者单独接受免疫治疗，10 例（7%）患者接受化疗-免疫治疗。我们分别分析了接受免疫治疗的患者和接受化疗-免疫治疗的患者。
与接种后 3 周相比，6 个月时的 T 细胞反应中位数明显降低[50 个四分位距（IQR）20-118.8 与 175 IQR 67.5-371.3 IFN-γ产生细胞/10 个外周血单个核细胞；P<0.0001]。SARS-CoV-2 初治患者的免疫球蛋白 G 浓度中位数下降 88%，SARS-CoV-2 既往感染患者下降 2.1%。SARS-CoV-2 NT Ab 滴度在 SARS-CoV-2 既往感染患者中保持稳定，而 SARS-CoV-2 初治患者中则显著下降（从中位数 1:160（IQR 1:40-1:640）至中位数 1:20（IQR 1:10-1:40）；P<0.0001）。在接种后 6 个月和 3 周时，SARS-CoV-2 NT Ab 滴度与刺突特异性 IFN-γ产生细胞之间均观察到弱相关性（r=0.467；P=0.0002 和 r=0.428；P=0.0006）。
我们的工作强调了癌症患者免疫反应的下降，特别是在 SARS-CoV-2 初治患者中。我们的数据支持对接受程序性细胞死亡蛋白 1/程序性死亡配体 1 抑制剂治疗的癌症患者给予第三剂 COVID-19 疫苗。
