The effect of liver metastasis on efficacy of immunotherapy plus chemotherapy in advanced lung cancer

Qin, Bao‐Dong; Jiao, Xiao‐Dong; Lee, Jun; Liu, Ke; He, Xi; Wu, Ying; Ling, Yan; Duan, Xidong; Qin, Wenxing; Wang, Zhan; Zang, Yuan‐Sheng

doi:10.1016/j.critrevonc.2020.102893

Cited by 40 publications

(37 citation statements)

References 33 publications

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“…[24,25] This tolerance may be related to incomplete CD8 + T-cell activation or effector T-cell inactivation, CD4 + T-cell inactivation and regulatory T-cell activation induced by Kupffer cells. [26] In our study, a higher PD-L1 level in liver metastases suggested that PD-L1 expression might also be involved in liver tolerance. However, combining the relative resistance to PD-1/PD-L1 inhibitors in patients with liver metastasis, we proposed that the ability of PD-1/PD-L1 inhibitors to enhance the immune system's response may be partially counteracted by other mechanisms of liver tolerance, thus compromising the effectiveness of treatment.…”

Section: Discussionsupporting

confidence: 53%

PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

Wei

Luo

Sheng

et al. 2020

Preprint

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Background: The outcomes of immune checkpoint inhibitors of patients with cancer liver metastases are poor, which may be related to a different tumor microenvironment from primary cancers. This study was aimed to analyze the PD-L1 expression and the immune microenvironment status in liver metastatic diseases and compare the differences of PD-L1 expression between primary tumors and liver metastases of colorectal cancer.Methods: 74 cases of pathologically confirmed colorectal cancer liver metastasis underwent resection from our hospital were included. Tissue microarrays were used for the interpretation of PD-L1 expression, cluster of differentiation 4 (CD4) and CD8 density by immunohistochemistry. Then, we evaluated the disparity between primary tumor and liver metastasis in PD-L1, CD4 and CD8 density and analyzed the factors associated with obvious disparity.Results: A total of 74 paired colorectal cancer with liver metastases were included in this study. The expression of PD-L1 in liver metastases was positively related to the density of CD4 and CD8. The expression of PD-L1 was higher in liver metastases than in primary tumors in certain subgroups of colorectal cancer, including the patients with concurrent liver metastases (n=63, p=0.05), receiving concurrent resection of primary and metastatic tumors (n=56, p=0.04). The two subgroups generally reflected those without inconsistent external influencing factors, such as treatment and temporal variation, between primary tumors and liver metastases. In these subgroups, the intrinsic differences of microenvironment between primary tumors and liver metastases could be identified, if any. Furthermore, tumor differentiation (moderate vs. poor: OR=0.23, 95% CI: 0.03-0.99, p=0.05)) were demonstrated to be associated with obvious discordance of PD-L1 expression between primary tumors and hepatic metastases.Conclusions: The expression of PD-L1 in the hepatic metastases was higher than in the primary tumors in subgroups reflecting intrinsic microenvironment differences between primary and metastatic tumors. Obvious discordance of PD-L1 expression between primary tumor and liver metastasis was closely related to the tumor differentiation.

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Section: Discussionsupporting

confidence: 53%

PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

Wei

Luo

Sheng

et al. 2020

Preprint

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“…On the one hand, there are a large number of immune cells in the liver that can activate the immune response against pathogens that may harm the organism rapidly, and on the other hand, the liver needs to suppress the overreaction of the immune system through certain mechanisms in order to maintain the stability of the internal environment [24,25]. This tolerance may be related to incomplete CD8 + T-cell activation or effector T-cell inactivation, CD4 + T-cell inactivation and regulatory T-cell activation induced by Kupffer cells [26]. In our study, a higher PD-L1 level in liver metastases suggested that PD-L1 expression might also be involved in liver tolerance.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

et al. 2020

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Background The outcomes of immune checkpoint inhibitors in cancer patients with liver metastases are poor, which may be related to a different tumor microenvironment in liver metastases from primary tumors. This study was aimed to analyze PD-L1 expression and the immune microenvironment status in liver metastases and compare the differences of PD-L1 expression between primary tumors and liver metastases of colorectal cancer. Methods 74 cases of pathologically confirmed colorectal cancer with liver metastasis underwent resection from our hospital were included. Tissue microarrays were used for the interpretation of PD-L1 expression, cluster of differentiation 4 (CD4) and CD8 density by immunohistochemistry. We evaluated the disparity between primary tumor and liver metastasis in PD-L1 expression, CD4 and CD8 density and analyzed the factors associated with obvious PD-L1 disparity. Results The expression of PD-L1 was positively related to the density of CD4 and CD8 in liver metastases. The expression of PD-L1 in liver metastases was higher than in primary tumors in certain subgroups, including patients with concurrent liver metastases (n = 63, p = 0.05), patients receiving concurrent resection of primary and metastatic tumors (n = 56, p = 0.04). The two subgroups generally reflected those without inconsistent external influences, such as treatment and temporal factors, between primary tumors and liver metastases. In these subgroups, the intrinsic differences of microenvironment between primary tumors and liver metastases could be identified. Furthermore, tumor differentiation [moderate vs. poor: OR = 0.23, 95% CI: 0.03–0.99, p = 0.05)] were demonstrated to be associated with obvious discordance of PD-L1 expression between primary tumors and liver metastases. Conclusions The expression of PD-L1 in liver metastases was higher than in primary tumors in subgroups, reflecting intrinsic microenvironment differences between primary and metastatic tumors. Obvious discordance of PD-L1 expression between primary tumor and liver metastasis was significantly related to the tumor differentiation.

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“…Tumeh et al [32] found that liver metastasis was associated with reduced marginal CD8 + T cell infiltration, which might be a potential mechanism for reduced response to immune checkpoint inhibitors (ICIs) monotherapy. In contrast, a meta-analysis [33] showed that there was no significant correlation between liver metastasis in patients with advanced lung cancer and the efficacy of immunotherapy combined with chemotherapy as first-line therapy; in other words, patients with and without liver metastasis in advanced lung cancer could get similar benefits from this treatment. Unfortunately, the specific mechanism of this phenomenon is still unclear.…”

Section: Discussionmentioning

confidence: 90%

Tumor Primary Location May Affect Metastasis Pattern for Patients with Stage IV NSCLC: A Population-Based Study

Shan

Lin

et al. 2020

Journal of Oncology

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Background. Most patients with nonsmall cell lung cancer (NSCLC) were initially diagnosed with distant metastasis. At present, there is no study to clarify the correlation between the primary location of the tumor and the metastasis pattern in advanced NSCLC. So we conducted this study to explored the relationship between the tumor primary location and metastasis pattern in stage IV NSCLC. Methods. A total of 19,295 eligible patients were identified from 2010 to 2012 in the SEER database. The main endpoint of our study was overall survival (OS). The survival curves were created by using the Kaplan–Meier method and compared by the usage of the Log Rank test. The clinical variable characteristics were compared by the chi-square test, and multivariate logistic regression analyses were used to evaluate the risk factors on metastasis patterns. All statistical P values were two-sided, and it was considered statistically significant when P≤0.05. Results. We found that different proportions of metastatic sites could be found in different tumor primary locations. In addition, the prognosis of lung metastasis was relatively good in patients with tumor location in main bronchus P<0.001, upper lobe P<0.001, lower lobe P<0.001 , and middle lobe P=0.005. Besides, there was no significant OS difference for patients whose primary location was overlapping lesion P=0.226. The results also demonstrated that compared with patients with primary tumor located in the main bronchus, those in the upper lobe were more likely to have brain metastasis P=0.01 and lung metastasis P=0.024, those in the middle lobe were more prone to develop lung metastasis P=0.035 and those in the lower lobe were more apt to cause bone metastasis P=0.005 and lung metastasis P=0.001. In addition, there was no statistical difference in metastasis patterns among patients with overlapping lesions P>0.05. Conclusions. Different primary tumor locations might affect the metastasis pattern in patients with stage IV NSCLC.

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The effect of liver metastasis on efficacy of immunotherapy plus chemotherapy in advanced lung cancer

Cited by 40 publications

References 33 publications

PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

Tumor Primary Location May Affect Metastasis Pattern for Patients with Stage IV NSCLC: A Population-Based Study

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