The prognostic value of a 4-factor neoimmunologic score system in non-small cell lung cancer
Summary Sentence: A neoimmunologic score system was constructed based on 4 variables including CD3+, CD8+, FoxP3+, and PD-1+ immune cell densities in non-small cell lung cancer.
The role of distinct immune cell types in modulating cancer progression has recently gained attention. The immune context is indicated by the abundance of immune infiltration based on quantified lymphocytes in the core of tumors (CT) and invasive tumor margin (IM). Novel immune biomarkers could potentially complement tumor-node-metastasis (TNM) classification for non-small cell lung cancers (NSCLCs), thereby improving prognostic accuracy. This study evaluated the prognostic value of a newly established immunologic score (neo-IS) in patients with NSCLC. We detected 10 immune biomarkers, including CD45RO, CD3, CD8, CD68, CD163, CD66b, FoxP3, PD-1, PD-L1, and TIM-3, in 350 patients with NSCLC from 2 cohorts using immunohistochemistry (IHC). The 3- and 5-year survival and overall survival (OS) rates were evaluated. An immunologic prediction model specifically for NSCLC patients, the neo-immunologic score (neo-ISNSCLC), was constructed using a Cox proportional hazards regression model. In the discovery cohort (n = 250), the establishment of neo-ISNSCLC was based on 4 immune biomarkers: CD3+IM, CD8+CT, FoxP3+IM, and PD-1+IM. Significant prognostic differences were found upon comparing low-ISNSCLC patients and high-ISNSCLC patients. The OS rate in the high-ISNSCLC group was significantly longer than that in the low-ISNSCLC group (67.5 months vs. 51.2 months, p < 0.001). The neo-ISNSCLC was validated in the validation cohort (n = 100), and the results were confirmed. Multivariate analyses indicated that neo-ISNSCLC was an independent indicator of prognosis in patients with NSCLC. Finally, we combined neo-ISNSCLC with clinicopathologic factors to establish a tumor-node-metastasis-immune (TNM-I) staging system for clinical use, which showed better prediction accuracy than the TNM stage.
The authors have no potential conflicts of interest to declare.
- 1, , , , , . Global cancer statistics 2018: gLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68: 394-424.
- 2, , . Lung cancer. Med Clin North Am. 2019; 103: 463-73.
- 3, , , et al. Non-small-cell lung cancer. Nat Rev Dis Primers. 2015; 1:15009.
- 4, , , . The eighth edition lung cancer stage classification. Chest. 2017; 151: 193-203.
- 5, , . Lung cancer staging and prognosis. Cancer Treat Res. 2016; 170: 47-75.
- 6, , . The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res. 2007; 67: 1883-6.
- 7, , , et al. ImmunoScore signature: a prognostic and predictive tool in gastric cancer. Ann Surg. 2018; 267: 504-13.
- 8, . Immunoscore for (colorectal) cancer precision medicine. Lancet. 2018; 391: 2084-6.
- 9, , , et al. A four-factor immunoscore system that predicts clinical outcome for stage II/III gastric cancer. Cancer Immunol Res. 2017; 5: 524-34.
- 10, , , . Tumor immunosurveillance in human cancers. Cancer Metastasis Rev. 2011; 30: 5-12.
- 11, , , . The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity. 2013; 39: 11-26.
- 12, , , et al. Cancer classification using the Immunoscore: a worldwide task force. J Transl Med. 2012; 10: 205.
- 13, , , et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol. 2014; 232: 199-209.
- 14, , , et al. Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer. Am J Respir Crit Care Med. 2014; 189: 832-44.
- 15, , , et al. Objective measurement and clinical significance of TILs in non-small cell lung cancer. J Natl Cancer Inst. 2015; 107.
- 16, , , , , . Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res. 2008; 14: 5220-7.
- 17, , , et al. Strategies for clinical implementation of TNM-Immunoscore in resected nonsmall-cell lung cancer. Ann Oncol. 2016; 27: 225-32.
- 18, , , et al. The non-small cell lung cancer immune contexture. A major determinant of tumor characteristics and patient outcome. Am J Respir Crit Care Med. 2015; 191: 377-90.
- 19, , , , , . Presence of CD3+ tumor infiltrating lymphocytes is significantly associated with good prognosis in infiltrating ductal carcinoma of breast. Indian J Cancer. 2013; 50: 239-44.
- 20, , , et al. Intratumoral CD3 and CD8 T-cell densities associated with relapse-free survival in HCC. Cancer Immunol Res. 2016; 4: 419-30.
- 21, , , et al. Associations between tissue-based CD3+ T-lymphocyte count and colorectal cancer survival in a prospective cohort of older women. Mol Carcinog. 2021; 60: 15-24.
- 22, , , et al. PD-1 and PD-L1 expression in NSCLC indicate a favorable prognosis in defined subgroups. PLoS One. 2015; 10:e0136023.
- 23, , , et al. PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma. Lung Cancer. 2015; 89: 181-8.
- 24, , , et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015; 112: 95-102.
- 25, , , , . High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol. 2011; 28: 682-8.
- 26, , . Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study. Tumori. 2012; 98: 751-5.
- 27, , , et al. B7-H1 and B7-H3 are independent predictors of poor prognosis in patients with non-small cell lung cancer. Oncotarget. 2015; 6: 3452-61.
- 28, , , et al. Assessing PDL-1 and PD-1 in non-small cell lung cancer: a novel immunoscore approach. Clin Lung Cancer. 2017; 18: 220-33 e8.