Serum IL-5 and IFN-γ Are Novel Predictive Biomarkers for Anti-PD-1 Treatment in NSCLC and GC Patients
Qiu Zhao, Yanzhi Bi, Huiting Sun, Min Xiao
Abstract
Background. Because responses of patients with cancer to immunotherapy can vary in success, effective biomarkers are urgently needed for predicting clinical response with anti-PD-1 treatment. We aimed to evaluate the IL-5 and IFN-γ level with the response of anti-PD-1 blockade in non-small-cell lung cancer (NSCLC) and gastric cancer (GC). Methods. Metastatic NSCLC and GC patients treated with anti-PD-1 monoclonal antibody were studied. Blood samples were taken before PD-1 McAb treatment, after the first cycle treatment, and during efficacy evaluation. The association between IL-5 and IFN-γ levels and clinical response were analyzed by the nonparametric Wilcoxon matched-pairs ranked tests. The progression-free survival (PFS) time was obtained by imaging evaluation and telephone follow-up of all the patients. Kaplan-Meier and the log rank test were used to plot the survival curve. Results. IL-5 and IFN-γ levels were detected in the peripheral blood of 40 NSCLC and 35 GC patients who have received anti-PD-1 treatment. In effective group, IL-5 and IFN-γ levels at best response points significantly decreased ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"><a:mi>P</a:mi><a:mo><</a:mo><a:mn>0.001</a:mn></a:math> ) compared with pretherapeutic levels in NSCLC and GC patients with lymph node or distant metastasis. Compared with pretherapeutic levels, IL-5 and IFN-γ levels largely increased as the tumor progresses ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"><c:mi>P</c:mi><c:mo><</c:mo><c:mn>0.01</c:mn></c:math> ). Higher IL-5 and IFN-γ levels before treatment indicated shorter progression-free survival in patients with NSCLC metastasis ( <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"><e:mi>P</e:mi><e:mo>=</e:mo><e:mn>0.007</e:mn></e:math> , <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"><g:mi>P</g:mi><g:mo>=</g:mo><g:mn>0.0111</g:mn></g:math> ). Moreover, their levels also accurately reflected the pseudoprogression of two NSCLC patients to anti-PD-1 treatment. Conclusions. Our results suggested that serum IL-5 and IFN-γ levels could be an effective indicator for predicting clinical efficacy and survival with anti-PD-1 blockade in NSCLC and GC patients.