A Pilot Study of Whether the Cold-Heat Syndrome Type is Associated with Treatment Response and Immune Status in Patients with Non-Small Cell Lung Cancer

Abstract

The cold-heat syndrome type (ZHENG) is one of the essential elements of syndrome differentiation in East Asian Medicine. This pilot study aimed to explore the characteristics of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) based on the cold-heat syndrome type. Twenty NSCLC patients treated with ICI monotherapy were included in the study and completed the cold-heat syndrome differentiation questionnaire. Demographic and clinical characteristics of the included patients were obtained through electronic medical records. Additionally, blood samples of 10 patients were analyzed with cytokine level and immune profiling. Patients were divided into two groups of cold type (n = 9) and non-cold type (n = 11), according to the cold symptoms questionnaire’s cutoff point. No significant difference between the two groups was observed in clinical response to ICIs ( p = 0.668 ). Progression-free survival (PFS) seemed to be longer in patients with non-cold type than cold type ( p = 0.332 ). In patients with adenocarcinoma, the non-cold type showed longer PFS than the cold type ( p = 0.036 ). Also, there were more patients with PD-L1 negative in the cold type compared to the non-cold type ( p = 0.050 ). In immune profiling, the proportion of effector memory CD8 T-cells was higher in patients with cold type than with non-cold type ( p = 0.015 ), and the proportion of terminal effector CD8 T-cells was lower in patients with cold type than with non-cold type ( p = 0.005 ). This pilot study has shown the potential for differences in prognosis and immune status between patients with cold and non-cold types. Hopefully, it provides essential information and insight into NSCLC patients’ characteristics from the perspective of syndrome differentiation. Further large-scale observational studies and intervention studies are required.

Genome-wide Analysis Identified SEMA4D, Novel Candidate Gene for Temperature Sensitivity in Patients With Non-Small Cell Lung Cancer

“… 34 Previously, patients with NSCLC and CPs were reported to be poorly responsive to ICIs because they had a relatively small number of active CD8 T cells based on immune profiling assay in the blood. 13 In the patients with NSCLC herein, CRP was slightly higher in HP group, and our genomic analysis suggested that a higher heat score increases the expression of SEMA4D for cancer progression. Taken together, temperature sensitivity indicates the immune status for cancer progression and may be used as a prognostic or predictive marker for ICIs in NSCLC.…”

“…12 Interestingly, immune checkpoint inhibitors (ICIs) significantly prolonged the progression-free survival (PFS) in patients with NSCLC and non-CP than those with CP. 13 Moreover, patients with NSCLC and CP rather than HP were more likely to have epidermal growth factor receptor (EGFR) gene mutations. 14 …”

Novel Biomarkers in Lung Cancer and Chronic Lung Diseases: From the Systematic Perspective of Yin–Yang Balance

“…The cold–heat pattern identification, representing the principle of Yin and Yang , is used as a basic diagnosis in clinical fields. Significant differences have been reported for immune status and treatment response based on the cold–heat patterns in patients with NSCLC treated with ICIs [ 20 ].…”