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Archive > Volume 29 Issue 12 > 2022,29(12):1108-1114. DOI:10.3872/j.issn.1007-385X.2022.12.007 Prev Next
Clinical Research
Tumor-associated macrophages and CD8+/CD68+ cell ratio are independent risk factors affecting the prognosis of lung adenocarcinoma patients
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Abstract:
Objective: To investigate the distribution of CD68+ tumor-associated macrophages (TAM), CD8+ T cells, Foxp3+ Treg cells, and other immune cells infiltrating lung adenocarcinoma (LUAD) tissues and their associations with patient prognosis. Methods: Ninety-three cases of LUAD tissues and 78 cases of paraneoplastic tissues surgically resected at the Third Affiliated Hospital of Soochow University between September 2004 and April 2009 were collected. The immune cell infiltration and distribution were detected by tissue microarray (TMA) and multiplex immunofluorescence (mIF) techniques. The Wilcoxon rank sum test was used to compare the differences in infiltration levels between cancer and paraneoplastic tissues, and between cancer nests and interstitial tissues. χ2 test was employed to analyze the relationship between their infiltration levels, CD8+/CD68+ cell ratios and clinicopathological features. Kaplan-Meier method and COX model were used to analyze the potential risk factors affecting patients' OS. Results: The infiltration levels of CD68+ TAM, CD8+ T cells, and Foxp3+ Treg cells in cancer tissues were significantly higher than those in paraneoplastic tissues (all P<0.01) while the infiltration levels of CD68+ TAM and CD8+ T cells in the interstitial tissues were significantly higher than that in the cancer nests (all P<0.01). The levels of total CD68+ TAM, cancer nest and interstitial CD68+ TAM infiltration were positively correlated with lymph node metastasis (all P<0.05); the levels of CD68+ TAM infiltration in cancer nests were positively correlated with T stage (P<0.05), and the levels of interstitial CD68+ TAM infiltration were positively correlated with pathological grading (P<0.05); the CD8+/CD68+ cell ratio in cancer tissues was negatively correlated with pathological grading and lymph node metastasis (all P<0.05). Kaplan-Meier survival analysis showed that the OS of patients with high infiltration of total CD68+ TAM, cancer nests and interstitial CD68+ TAM in LUAD tissues was shorter than that of patients with low infiltration (P<0.05 or P<0.01), and the OS of patients with high CD8+/CD68+ cell ratio in cancer tissues was significantly longer than that of patients with low ratio (P<0.05). Multivariate COX model analysis showed that age, TNM stage and CD8+/CD68+ cell ratio in cancer tissues were independent risk factors for the prognosis of LUAD patients (P<0.05 or P<0.01). Conclusion: Highly infiltrative CD68+ TAM was significantly associated with the progression, invasion, metastasis and poor prognosis of LUAD, and a high CD8+/CD68+ cell ratio was an independent protective factor for the OS of patients with LUAD.
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