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

Overview

Journal Target Oncol

Specialty Oncology

Date 2023 Jun 23

PMID 37351800

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

Affiliations

Soon will be listed here.

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/mm, p = 0.028; percentage: median 3.53% vs. 15.92%, p = 0.028) and CD4 cells (density: median 275.56 vs. 651.82 cells/mm, p = 0.028; percentage: median 5.98% vs. 10.46%, p = 0.028). Similar results were found for CD4FOXP3, CD8PD1, CD8PD1, CD8GB, and CD8GB cells. However, macrophages, including CD68CD163 M1 and CD68CD163 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.

Citing Articles

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PMID: 40071084 PMC: 11893432. DOI: 10.3389/fonc.2025.1474997.

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Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions.

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