BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontin...BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.展开更多
Hepatocellular carcinoma(HCC)is one of the deadliest and most common malignancies of the liver.Considering the rich immune background of carcinogenesis in HCC,efforts have been focused on further understanding the rol...Hepatocellular carcinoma(HCC)is one of the deadliest and most common malignancies of the liver.Considering the rich immune background of carcinogenesis in HCC,efforts have been focused on further understanding the role of the immune system in tumor suppression and promotion.The utilization of immunotherapy in HCC has led to encouraging results that has translated to longer survival and better quality of life among patients.The development of novel HCC-tailored regimens such as vaccine therapy and adoptive cellular therapy coupled with a deeper understanding of biomarkers predictive of the response to immunotherapy will lead to better treatment outcomes.展开更多
Colorectal cancer(CRC)is the second deadliest malignancy for both sexes.The BRAF^(V600E)mutation,one of the most common driver mutations in CRC,is known for its poor prognosis due to the increased risk of metastasis.T...Colorectal cancer(CRC)is the second deadliest malignancy for both sexes.The BRAF^(V600E)mutation,one of the most common driver mutations in CRC,is known for its poor prognosis due to the increased risk of metastasis.The effect of the BRAF^(V600E)mutation on the tumor microenvironment was the topic of the study reported in World Journal of Gastrointestinal Oncology,with special focus on immune status.The authors presented insightful findings that were exclusively based on macrophage polarity and cytokine levels,without investigating other relevant immune elements.A more comprehensive look into the dynamic immune activity of cancer environments will warrant more meaningful practical findings.In this letter,we discuss other significant immune factors and their possible implications on the tumor microenvironment of BRAF-mutated CRC.展开更多
文摘BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.
文摘Hepatocellular carcinoma(HCC)is one of the deadliest and most common malignancies of the liver.Considering the rich immune background of carcinogenesis in HCC,efforts have been focused on further understanding the role of the immune system in tumor suppression and promotion.The utilization of immunotherapy in HCC has led to encouraging results that has translated to longer survival and better quality of life among patients.The development of novel HCC-tailored regimens such as vaccine therapy and adoptive cellular therapy coupled with a deeper understanding of biomarkers predictive of the response to immunotherapy will lead to better treatment outcomes.
文摘Colorectal cancer(CRC)is the second deadliest malignancy for both sexes.The BRAF^(V600E)mutation,one of the most common driver mutations in CRC,is known for its poor prognosis due to the increased risk of metastasis.The effect of the BRAF^(V600E)mutation on the tumor microenvironment was the topic of the study reported in World Journal of Gastrointestinal Oncology,with special focus on immune status.The authors presented insightful findings that were exclusively based on macrophage polarity and cytokine levels,without investigating other relevant immune elements.A more comprehensive look into the dynamic immune activity of cancer environments will warrant more meaningful practical findings.In this letter,we discuss other significant immune factors and their possible implications on the tumor microenvironment of BRAF-mutated CRC.
