Characterization of the tumor immune-microenvironment of lung adenocarcinoma associated with usual interstitial pneumonia. (December 2018)

• Record Type: Journal Article
• Authors: Ueda, Takuya; Aokage, Keiju; Mimaki, Sachiyo; Tane, Kenta; Miyoshi, Tomohiro; Sugano, Masato; Kojima, Motohiro; Fujii, Satoshi; Kuwata, Takeshi; Ochiai, Atsushi; Kusumoto, Masahiko; Suzuki, Kenji; Tsuchihara, Katsuya; Nishikawa, Hiroyoshi; Goto, Koichi; Tsuboi, Masahiro; Ishii, Genichiro
• Is Part Of: Lung cancer. Volume 126(2018)
• Page Start: 162
• Page End: 169
• Publication Date: 2018-12
• Subjects: ADC adenocarcinoma -- ALDH-1 aldehyde dehydrogenase 1 -- CAFs cancer-associated fibroblasts -- CA IX carbonic anhydrase IX -- CD8 cluster of differentiation 8 -- CD204 cluster of differentiation 204 -- CSS cancer specific survival -- EGFR epidermal growth factor receptor -- Foxp3 forkhead boxprotein P3 -- HPF high power field -- IHC immunohistochemistry -- IPF idiopathic pulmonary fibrosis -- LVI lymphovascular invasion -- NSCLC non-small cell lung cancer -- OS overall survival -- PD-L1 programmed cell death ligand 1 -- RFS recurrence-free survival -- SqCC squamous cell carcinoma -- TAMs tumor associated macrophages -- TILs tumor infiltrating lymphocytes -- T-regs regular T-cells -- UIP usual interstitial pneumonia -- VPI visceral pleural invasion; Adenocarcinoma -- Idiopathic pulmonary fibrosis -- Usual interstitial pneumonia -- Tumor microenvironment -- Tumor infiltrating lymphocytes; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2018.11.006
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: UIP-ADC patients had worse prognosis than non-UIP ADC patients. UIP-ADC patients exhibited reduced levels of CD8 + TILs. The CD8 + /Foxp3 + T cell ratio was significantly reduced in UIP-ADC. The tumor microenvironment of UIP-ADC acquires an immunosuppressive state. Abstract: Background: Lung cancer with usual interstitial pneumonia (UIP) pattern is a disease with poor prognosis. This study aimed to characterize the tumor microenvironment of lung adenocarcinoma associated with UIP (UIP-ADC). Methods: A total of 1341 consecutive patients with ADC who had undergone complete surgical resection were enrolled in this study, and the clinicopathological features of UIP-ADC were examined. Further, we selected 17 cases of UIP-ADC and non-UIP ADC each (adjusted for age, smoking status, pathological stage, and invasive size of lesion) for immunohistochemical analysis, and the biological differences between UIP-ADC and non-UIP ADC groups were analyzed. Results: UIP-ADC was detected in 18 patients (1.3%). Patients with UIP-ADC had shorter cancer-specific survival (CSS) (5 yrs CSS; UIP-ADC 52.9% vs non-UIP ADC 81.8%, p < 0.01). Evaluation of tumor-infiltrating lymphocytes (TILs) in cancer stroma showed that the number of CD8 + TILs in UIP-ADC group was significantly lower than that in the non-UIP ADC group (median number 91 vs 121, p < 0.01). In contrast, levels of Foxp3 + TILs were not significantly different between the two groups. The CD8 + /Foxp3 + T cell ratio was significantly lower in UIP-ADC than in the non-UIP ADC population (1.9 vs 2.7, p < 0.01). Additionally, among UIP-ADC patients, the CD8 + /Foxp3 + T cell ratio was significantly higher in the non-cancerous UIP lesions than in the cancer stroma from the same patient (2.4 vs 1.7, p < 0.01). Conclusion: In the current study, we have demonstrated that the tumor microenvironment of UIP-ADC acquires an immunosuppressive state, and this could be one of the possible explanations for poor prognosis of this disease.