Non-Invasive Tumor Immune Dysfunction and Exclusion Evaluation and Chemoimmunotherapy Response Prediction in Lung Adenocarcinoma Using Pathomic-Based Approach

Background: Tumor Immune Dysfunction and Exclusion (TIDE) integrated the signatures of T-cell dysfunction and T-cell exclusion, and exhibited significant predictive performance for immune checkpoint inhibitors efficacy. This study investigated the correlation between pathomic model and TIDE, including its predictive value for chemoimmunotherapy treatment response in patients with lung adenocarcinoma (LUAD).Methods: The pathomic model was developed and validated in TCGA LUAD training and validation cohorts. We assessed its predictive value to chemoimmunotherapy in a cohort of patients with advanced LUAD. Gene set enrichment analysis (GSEA) was performed using transcriptome profiles to investigate the potential mechanism.Results: The pathomic model distinguished between High-TIDE and Low-TIDE patients in the training cohort (area under the curve (AUC): 0.81, 95% CI: 0.76-0.87)) and test cohort (AUC: 0.73, 95% CI: 0.63-0.83). This model was significantly associated with overall survival (OS) in TCGA LUAD cohort (HR = 1.53; 95% CI: 1.05-2.21, P = 0.025). In advanced LUAD patients treated with chemoimmunotherapy, the model predicted progression-free survival (PFS; HR = 0.37; 95% CI: 0.18-0.77; P = 0.008) and OS (HR = 0.27; 95% CI: 0.08-0.84; P = 0.024). Furthermore, this model improved predictive accuracy when combined with PD-L1 expression (AUC: 0.70, 95% CI: 0.55–0.85).Conclusions: The pathomic model can be used to assess TIDE status, prognosis and chemoimmunotherapy benefit of LUAD patients. The potential of pathomic model as a non-invasive predictor needed to be confirmed in future studies.Funding: This study was supported by National Natural Science Foundation of China (No. 82373425 and No. 82372722), the Medical Innovation Research Special Project of the Science and Technology Commission of Shanghai Municipality (No. 23Y11904200), Shanghai Innovative Medical Device Application Demonstration Project 2023 (No. 23SHS02600), the "Science and Technology Innovation Action Plan" Medical Innovation Research Special Project of Shanghai (No.21Y11913500), the key project of the Medical and Health Technology Development Research Center of the National Health Commission (No.WKZX2023CX030003), and the Shanghai Key Laboratory Open Project (No. STCSM 22DZ2229005).Declaration of Interest: All authors have declared no conflicts of interest.Ethical Approval: This study was approved by the Ethics Committee of Shanghai Chest Hospital (Institutional review board No. KS24007). Written informed consent was obtained from patients or their guardians.