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23-06-2023 | NSCLC | Original Research Article

Pathological Response and Tumor Immune Microenvironment Remodeling Upon Neoadjuvant ALK-TKI Treatment in ALK-Rearranged Non-Small Cell Lung Cancer

Authors: Nan Zheng, Yimin Zhang, Yue Zeng, Qiang Ma, Ruiguang Zhang, Qian Zhao, Conghua Lu, Jie Tian, ZhiGuo Wang, Huan Tang, Nuo Luo, Hualiang Xiao, Yong He, Fang Wu, Li Li

Published in: Targeted Oncology | Issue 4/2023

Abstract

Background

Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKI; ALKi) have shown potent antitumor activity in metastatic non-small-cell lung cancer (NSCLC) with ALK rearrangement (ALK+); however, their efficacy in neoadjuvant settings has been poorly explored.

Objective

This retrospective study aimed to examine the clinical activity and tumor immune microenvironment (TIME) changes of neoadjuvant ALKi therapy.

Methods

ALK+ NSCLC patients treated with neoadjuvant ALKi at three hospitals in China between February 2018 and January 2023 were assessed. Data on clinical features and radiographic and pathological responses were collected and evaluated. Multiplex immunofluorescence was performed on pretreatment biopsy specimens and surgically resected specimens to investigate the impact of ALKi on TIME.

Results

A total of 12 patients with stage IIA–IIIB NSCLC who received neoadjuvant ALKi therapy were analyzed. The objective response rate was 91.7% (11/12) and the major pathological response (MPR) rate was 75.0% (9/12), with 58.3% (7/12) achieving a pathological complete response (pCR). After neoadjuvant ALKi therapy, we observed a significant increase in immune infiltration of CD8⁺ cells (histochemistry score [H-score]: median 10.51 vs. 24.01, p = 0.028; density: median 128.38 vs. 694.09 cells/mm², p = 0.028; percentage: median 3.53% vs. 15.92%, p = 0.028) and CD4⁺ cells (density: median 275.56 vs. 651.82 cells/mm², p = 0.028; percentage: median 5.98% vs. 10.46%, p = 0.028). Similar results were found for CD4⁺FOXP3⁺, CD8⁺PD1⁺, CD8⁺PD1^-, CD8⁺GB⁺, and CD8⁺GB^- cells. However, macrophages, including CD68⁺CD163^- M1 and CD68⁺CD163⁺ M2 macrophages, showed little change after neoadjuvant ALKi therapy.

Conclusion

Neoadjuvant ALKi therapy achieved an encouraging MPR rate of 75% and enhanced immune infiltration, suggesting its safety and feasibility for ALK+ resectable NSCLC. This study advances our understanding of TIME changes by neoadjuvant ALKi therapy and merits further investigation.

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Title: Pathological Response and Tumor Immune Microenvironment Remodeling Upon Neoadjuvant ALK-TKI Treatment in ALK-Rearranged Non-Small Cell Lung Cancer
Authors: Nan Zheng
Yimin Zhang
Yue Zeng
Qiang Ma
Ruiguang Zhang
Qian Zhao
Conghua Lu
Jie Tian
ZhiGuo Wang
Huan Tang
Nuo Luo
Hualiang Xiao
Yong He
Fang Wu
Li Li
Publication date: 23-06-2023
Publisher: Springer International Publishing
Keywords: NSCLC
NSCLC
Crizotinib
Published in: Targeted Oncology / Issue 4/2023
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI: https://doi.org/10.1007/s11523-023-00981-7

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