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Objective To evaluate the prognosis-related factors of colorectal cancer patients with positive PD-L1 expression in liver metastases after hepatectomy. Methods We reviewed retrospectively the clinical data of 68 colorectal cancer patients with positive PD-L1 expression in liver metastases receiving personalized comprehensive treatment which was mainly consisted of surgical resection. We observed the results and prognosis after surgical resection and analyzed related factors. Results Univariate analysis showed that no radiotherapy, N stage, RAS mutation status, T stage, dMMR, Duck stage, disease free interval from primary to metastases≤12 months and largest hepatic tumor diameter > 5 cm had obvious significance (all P < 0.05). Multivariate logistic analysis regression revealed that without dMMR (P=0.012), Duck A stage (P=0.000), disease free interval from primary to metastases > 12 months (P=0.020) and largest hepatic tumor diameter < 5 cm (P=0.006) were independent protective factors for the prognosis of colorectal cancer patients with positive PD-L1 expression in liver metastases after surgical resection. Conclusion Personalized comprehensive treatment which is mainly consisted of surgical resection still has a good effect on colorectal cancer patients with positive PD-L1 expression in liver metastases after hepatectomy. Without dMMR, Duck A stage, disease free interval from primary to metastases > 12 months and largest hepatic tumor diameter ≤5cm are independent protective factors for patients' prognosis.
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Objective: In tumor microenvironment, immune-related mechanisms up-regulate the expression of programmed death li-gand 1 (PD-L1), which abnormally activates PD-L1 signaling pathway and mediates tumor immune escape. Soluble programmed death ligand 1 (sPD-L1) is a form of PD-L1. It has been confirmed that the expression of sPD-L1 in lung squamous cell carcinoma and adeno-carcinoma is related to disease progression, while small cell lung cancer (SCLC) has a high degree of malignancy, strong invasiveness and few related studies. The purpose of this study was to observe the changes in expression of sPD-L1 in the plasma of SCLC patients and their clinical significance. Methods: A total of 94 patients with SCLC diagnosed by pathological examination in Shanxi Provincial Cancer Hospital from March 2018 to November 2018 were selected as test group, and 17 healthy persons in the same period were se-lected as control group. The dynamic changes of plasma sPD-L1 were compared between the two groups, and the correlations among the expression of sPD-L1 and TNM stage, distant metastasis, and pro-gastrin-releasing peptide (ProGRP) was analyzed. Results: The lev-el of sPD-L1 in the test group was higher than that in the control group (P<0.05 and P<0.01, respectively). In patients with SCLC in the remission stage, the serum sPD-L1 level after chemotherapy was significantly lower than that before chemotherapy (P<0.01); in pa-tients with advanced stage, the serum sPD-L1 level after chemotherapy was significantly higher than that before chemotherapy (P<0.01). The abnormal high expression of sPD-L1 in SCLC patients was significantly correlated with the progression of the disease (P<0.05). The expression of sPD-L1 in serum was positively correlated with the tumor marker ProGRP. Conclusions: The expression of sPD-L1 in peripheral plasma of patients with SCLC is higher than that in healthy individuals and is closely related to the clinical effect.
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Small-cell lung cancer (SCLC) has a high degree of malignancy and is characterized by strong invasiveness, rapid growth, and early metastasis. SCLC is sensitive to initial treatment with chemotherapy and radiotherapy, but it can easily relapse and has a poor prognosis. Both programmed death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) antagonists activate the immune response of tumor cells by activating T cells, and have shown exciting curative effects in clinical studies of SCLC, thereby becoming powerful po-tential agents to treat SCLC in the future. This article aims to illustrate the progress of PD-1/PD-L1 inhibitors in the treatment of SCLC, as well as the role of PD-L1 expression and tumor mutation burden (TMB) as a biomarker in SCLC.
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Introdução: Os inibidores de checkpoint imunológico são drogas promissoras do campo da imunoterapia oncológica moderna. Entretanto, somete um grupo selecionado de pacientes apresenta benefício com tais terapias. Contudo, temse procurado por biomarcadores preditivos que possam auxiliar na tomada de decisão terapêutica. Os biomarcadores mais estudados são a expressão de PD-L1, a carga de mutação somática tumoral, e a presença de defeito nos genes do mismatch-repair do DNA ou de alta instabilidade microsatélite (MMRd/MSI-H). Métodos: Foram revisados os ensaios clínicos que dão suporte as evidências atuais para utilização dos inibidores de checkpoint imunológico na prática clínica. Resultados: A testagem de PD-L1 como biomarcador preditivo só é recomendada para o uso de Pembrolizumab no câncer de pulmão, e não se demonstrou papel preditivo para a expressão de PD-L1 no câncer colorretal e urotelial. Nas demais neoplasias a maior expressão de PD-L1 costuma se relacionar com aumento nas taxas de resposta e sobrevida, embora mesmo pacientes PD-L1 negativos se beneficiem das terapias anti-PD-1/ PD-L1. Apenas os estudos com Atezolizumab no câncer urotelial avaliaram a carga de mutação somática como biomarcador independente, que esteve relacionada com maior taxa de resposta objetiva e maior sobrevida global. O papel da imunoterapia no tratamento dos tumores MMRd/MSI-H ainda está sendo investigado, mas as evidências até então a apontam como uma opção terapêutica promissora para esse grupo de pacientes. Conclusão: Com exceção do câncer de pulmão, não há evidência para a testagem de PD-L1 como biomarcador na prática clínica. A avaliação da carga de mutação somática como biomarcador preditivo ainda é experimental. As evidências atuais sugerem que os pacientes portadores de neoplasias MMRd/MSI-H são candidatos ao tratamento com inibidores de checkpoint imunológico.
Introduction: The immune checkpoint inhibitors are promising drugs in the field of cancer immunotherapy. However, a selected population will derive benefit from this treatment strategy. Predictive biomarkers have been investigated in order to guide decisions making process. The three most studied biomarkers are the PD-L1 expression, the mutational load and the presence of DNA mismatch-repair defects or high microsatellite instability. Methods: The clinical trials that support the current recommendations for immune checkpoint inhibitors therapy were reviewed. Results: Testing for PD-L1 is only recommended prior to Pembrolizumab therapy in lung cancer, and the PD-L1 expression was not shown to be a predictive factor in urothelial and colorectal cancer. In other neoplasias, although the higher PD-L1 expression was likely to improve response or survival rates with PD-1/PD-L1 blockade, even the PD-L1 negative patients might benefit from these drugs. Only the clinical trials with Atezolizumab in urothelial cancer reported the higher somatic mutational load as independent predictive biomarker, and it was associated with higher response rates and longer overall survival. The role of immunotherapy in the treatment of MMR-d/MSI-H tumors is still being investigated, but the evidence so far support that it might be a promising therapeutical option for this subset of patients. Conclusions: Exception for lung cancer, testing for PD-L1 expression is not recommended in the clinical practice. Evaluating for somatic mutational burden is still experimental. The current evidence suggests that the patients with MMR-d/MSI-H tumors are candidates for immune checkpoint inhibition therapy.
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Biomarkers, Tumor , Immune Checkpoint Inhibitors , Mutation , NeoplasmsABSTRACT
Purpose To analyze the correlations between PD-L1 expression and clinicopathological factors and their prognostic values in esophageal squamous cell carcinoma (ESCC) patients.Methods PD-L1 expression in the primary tumors from 253 patients with ESCC was evaluated using tissue microarray and immunohistochemistry (IHC).PD-L1 positivity was defined as positive staining of 1％ and 5％ tumor cells.Survival curves were constructed by using the Kaplan-Meier method.Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables.Results Overall,tumoral PD-L1 expression was potentially associated with favorable DFS and OS.When the patients were stratified into stage Ⅰ + Ⅱ (60.9％,154/253) and stage Ⅲ + Ⅳa (39.1％,99/253),the prognostic role was not consistent.In patients with stage Ⅰ + Ⅱ disease,tumoral PD-L1 expression was associated with better DFS and OS upon multivariate analysis (1％ as the cutoff:P =0.046 and 0.021,5％ as the cutoff:P=0.011 and0.004).However,PD-L1 expression was not correlated with prognosis in patients with stage Ⅲ + Ⅳa disease (1％ as the cutoff:P =0.586 and 0.682,5％ as the cutoff:P =0.807 and 0.620).Conclusion The prognostic role of tumoral PDL expression is variable in different stages of ESCC,and tumoral PDL expression is an independent favorable predictor in ESCC patients with Stage Ⅰ-Ⅱ disease,but not in stage Ⅲ-Ⅳa or lymph node metastasis.