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Published on: July 28, 2020
Effect of neoadjuvant targeted therapy on the tumor microenvironment in resectable lung adenocarcinoma
Ling Yi1, Heng Yao2, Zhexin Bai3
1Department of Cancer Research Center, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Background:
Neoadjuvant targeted therapy has emerged as a promising strategy for resectable non-small cell lung cancer (NSCLC). The analysis of the immune status of tumor microenvironment (TME) after targeted therapies is crucial for understanding the impact of targeted therapy on the TME and providing a basis for synergistic therapeutic approaches.
Methods:
Forty-two patients with resectable lung adenocarcinoma (LUAD) were enrolled in this study, and multiplex immunofluorescence technology was used to explore the immune status of the TME after neoadjuvant targeted therapies.
Results:
Among the 42 patients, 9 (21.4%) and 33 (78.6%) had ALK and EGFR mutations, respectively, and TKIs were their first-line treatment. All patients received R0 resection, and thoracoscopic minimally invasive surgery were the predominant method. Seven (16.7%) patients reached pathological complete response (pCR), 4 (9.5%) get major pathological response (MPR), and these 11 patients were classified into the MPR group. The remaining 31 (73.8%) patients were non-MPR. The densities of CD8 + T cells (P < 0.001, P = 0.001), GZMB + CD8 + T cells (P = 0.004, P = 0.008), PD-1 + CD8 + T cells (P = 0.019, P = 0.036), macrophages (P = 0.020, P = 0.007), M1 macrophages (P = 0.010, P = 0.007), and ratios of CD8 + T/Treg (P < 0.001, P = 0.026) in TME were significantly higher in the MPR group and ALK mutation group compared with non-MPR and EGFR group. There were positive correlations between CD8 + T cells, PD-1 + CD8 + T cells (r = 0.397, P = 0.009) and GZMB + CD8 + T cells (r = 0.351, P = 0.023); CD8 + T cells and macrophages (r = 0.343, P = 0.026), and M1 macrophages (r = 0.412, P = 0.007). Additionally, eleven patients experienced disease progress during the follow-up period, and the Log-Rank test revealed that MPR patients tended to get longer PFS compared with non-MPR patients (P = 0.063), especially patients with higher densities of macrophages in the TME had significantly longer PFS (P = 0.042).
Conclusion:
TKI-targeted therapy could reduce tumor burden, facilitating complete surgical resection. Patients with MPR and ALK mutations had a higher density of inflammatory immune cells in the TME and those with higher densities of macrophage had significantly longer PFS.
Clinical Trial Number:
Not applicable.
Insights
Neoadjuvant targeted therapy in non-small cell lung cancer (NSCLC) increases immune cell density in the tumor microenvironment (TME). Patients with major pathological response (MPR) and ALK mutations show higher immune cell infiltration and improved survival.
Area of Science:
- Oncology
- Immunology
- Thoracic Surgery
Background:
- Neoadjuvant targeted therapy is a promising strategy for resectable non-small cell lung cancer (NSCLC).
- Analyzing the tumor microenvironment (TME) immune status post-targeted therapy is crucial for understanding treatment impact and developing synergistic approaches.
Purpose of the Study:
- To investigate the immune status of the TME after neoadjuvant targeted therapies in patients with resectable lung adenocarcinoma (LUAD).
- To correlate TME immune cell infiltration with pathological response and patient outcomes.
Main Methods:
- Forty-two patients with resectable LUAD received neoadjuvant targeted therapy (TKIs for ALK/EGFR mutations).
- Multiplex immunofluorescence technology was employed to analyze TME immune cell composition.
- Pathological response (pCR, MPR) and progression-free survival (PFS) were assessed.
Main Results:
- Patients achieving major pathological response (MPR) and those with ALK mutations exhibited significantly higher densities of CD8+ T cells, GZMB+ CD8+ T cells, PD-1+ CD8+ T cells, macrophages, and M1 macrophages compared to non-MPR and EGFR groups.
- Positive correlations were observed between CD8+ T cells and various immune markers, as well as between CD8+ T cells and macrophage populations.
- MPR patients showed a trend towards longer PFS, and higher macrophage density in the TME was significantly associated with longer PFS.
Conclusions:
- TKI-targeted therapy effectively reduces tumor burden, facilitating complete surgical resection.
- MPR and ALK mutations are associated with increased inflammatory immune cell density in the TME.
- Higher macrophage density in the TME correlates with significantly longer progression-free survival.
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