RESUMO
OBJECTIVE: To observe the effect of thymalfasin on myeloid-derived suppressor cells (MDSCs) subsets in peripheral blood of patients with non-small cell lung cancer (NSCLC). METHODS: 50 cases of NSCLC (NSCLC group) diagnosed in Chest Hospital of Jiangxi Province were selected as the research subjects, and 50 healthy subjects who underwent physical examination in our hospital during the same period were selected as the healthy control group. The expression of HLA-DR-CD14-CD33+ MDSCs in peripheral blood mononuclear cells and tumor tissue single cell suspension of NSCLC patients before and after thymalfasin treatment was explored by flow cytometry. RESULTS: The proportion of MDSCs in peripheral blood of NSCLC group was 1.70±0.52%, which was significantly higher than that in peripheral blood (0.51±0.15%) of healthy controls (P < 0.05). The proportion of HLA-DR-CD14-CD33+ MDSCs in the tissues of NSCLC group was 1.65±0.43% before treatment and 1.15±0.50% after treatment (P < 0.05). The proportion of MDSCs in peripheral blood of NSCLC patients before treatment was 1.70±0.52%, and that after treatment was 0.59±0.18% (P < 0.05). CONCLUSION: Thymalfasin can reduce the number of MDSCs in peripheral blood mononuclear cells. The application of thymalfasin in the treatment of NSCLC patients can help to enhance the anti-tumor effect.
RESUMO
BACKGROUND: The response rate to immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) receptor is 13%-18% for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Detailed understanding of the tumor immune microenvironment (TIME) is crucial in order to explain and improve this response rate. HNSCCs arise at various anatomical locations including the oral cavity, hypopharynx, larynx and oropharynx. Studies directly comparing immune infiltration between anatomical sites are scarce. Since the distinct locations could drive deviating microenvironments, we questioned whether the immune composition varies across these HNSCC sites. METHODS: Here, we characterized the TIME of 76 fresh tumor specimens using flow cytometry and performed single-cell RNA-sequencing on nine head and neck tumor samples. RESULTS: We found major differences in the composition of the TIME between patients. When comparing anatomical sites: tumors originating from the oral cavity had higher T cell infiltrates than tumors from other anatomical sites. The percentage of tumor-infiltrating T-lymphocytes positive for the immune checkpoint PD-1 varied considerably between patients, with the highest fraction of PD-1+ T cells found in larynx squamous cell carcinomas (SCCs). While we had hypothesized that the anatomical sites of tumor origin would drive sample clustering, our data showed that the type of TIME was more dominant and was particularly driven by the fraction of T cells positive for PD-1. Moreover, a high proportion of PD-1+ CD8+ T cells associated with an improved overall survival. Using single-cell RNA-sequencing, we observed that PD-1 expression was highest in the CD8-ENTPD1 tissue resident memory T cell/exhausted T cell and CD4-CXCL13 type 1 T helper cell clusters. CONCLUSIONS: We found that oral cavity SCCs had the highest frequencies of T cells. We also observed considerable interpatient heterogeneity for PD-1 on T cells, with noticeably higher frequencies of PD-1+ CD4+ T helper cells in larynx SCCs. Within the entire cohort, a higher fraction of CD8+ T cells positive for PD-1 was linked to improved overall survival. Whether the fraction of PD-1+ T cells within the TIME enables immune checkpoint inhibitor response prediction for patients with head and neck cancer remains to be determined.