Objective: The Immunoscore method has proved fruitful for predicting prognosis in patients with colon cancer.However, there is still room for improvement in this scoring method to achieve further advances in its clini...Objective: The Immunoscore method has proved fruitful for predicting prognosis in patients with colon cancer.However, there is still room for improvement in this scoring method to achieve further advances in its clinical translation. This study aimed to develop and validate a modified Immunoscore(IS-mod) system for predicting overall survival(OS) in patients with stage Ⅰ-Ⅲ colon cancer.Methods: The IS-mod was proposed by counting CD3+ and CD8+ immune cells in regions of the tumor core and its invasive margin by drawing two lines of interest. A discovery cohort(N=212) and validation cohort(N=103)from two centers were used to evaluate the prognostic value of the IS-mod.Results: In the discovery cohort, 5-year survival rates were 88.6% in the high IS-mod group and 60.7% in the low IS-mod group. Multivariate analysis confirmed that the IS-mod was an independent prognostic factor for OS[adjusted hazard ratio(HR)=0.36, 95% confidence interval(95% CI): 0.20-0.63]. With less annotation and computation cost, the IS-mod achieved performance comparable to that of the Immunoscore-like(IS-like) system(C-index, 0.676 vs. 0.661, P=0.231). The 2-category IS-mod using 47.5% as the threshold had a better prognostic value than that using a fixed threshold of 25%(C-index, 0.653 vs. 0.573, P=0.004). Similar results were confirmed in the validation cohort.Conclusions: Our method simplifies the annotation and accelerates the calculation of Immunoscore method,thus making it easier for clinical implementation. The IS-mod achieved comparable prognostic performance when compared to the IS-like system in both cohorts. Besides, we further found that even with a small reference set(N≥120), the IS-mod still demonstrated a stable prognostic value. This finding may inspire other institutions to develop a local reference set of an IS-mod system for more accurate risk stratification of colon cancer.展开更多
Objective:Pretreatment prediction of Immunoscore in patients with hepatocellular cancer(HCC)is important for precision immunotherapy.We aimed to develop a radiomics model based on gadolinium-ethoxybenzyl-diethylenetri...Objective:Pretreatment prediction of Immunoscore in patients with hepatocellular cancer(HCC)is important for precision immunotherapy.We aimed to develop a radiomics model based on gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid(Gd-EOB-DTPA)-enhanced magnetic resonance imaging(MRI)for pretreatment prediction of Immunoscore(0-2 vs.3-4)in HCC.展开更多
In this editorial we comment on the article by Agatsuma et al published in the World Journal of Gastroenterology.They suggest policies for more effective colorectal screening.Screening is the main policy that has led ...In this editorial we comment on the article by Agatsuma et al published in the World Journal of Gastroenterology.They suggest policies for more effective colorectal screening.Screening is the main policy that has led to lower mortality rates in later years among the population that was eligible for screening.Colonoscopy is the gold standard tool for screening and has preventive effects by removing precancerous or early malignant polyps.However,colonoscopy is an invasive process,and fecal tests such as the current hemoglobin immunodetection were developed,followed by endoscopy,as the general tool for population screening,avoiding logistical and economic problems.Even so,participation and adherence rates are low.Different screening options are being developed with the idea that if people could choose between the ones that best suit them,participation in population-based screening programs would increase.Blood tests,such as a recent one that detects cell-free DNA shed by tumors called circulating tumor DNA,showed a similar accuracy rate to stool tests for cancer,but were less sensitive for advanced precancerous lesions.At the time when the crosstalk between the immune system and cancer was being established as a new hallmark of cancer,novel immune system-related biomarkers and information on patients’immune parameters,such as cell counts of different immune populations,were studied for the early detection of colorectal cancer,since they could be effective in asymptomatic people,appearing earlier in the adenoma-carcinoma development compared to the presence of fecal blood.sCD26,for example,detected 80.37%of advanced adenomas.To reach as many eligible people as possible,starting at an earlier age than current programs,the direction could be to apply tests based on blood,urine or salivary fluid to samples taken during routine visits to the primary health system.展开更多
Colorectal cancer(CRC)represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death worldwide.The traditional classification of CRC is based on pathomorphological and molec...Colorectal cancer(CRC)represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death worldwide.The traditional classification of CRC is based on pathomorphological and molecular character-istics of tumor cells(mucinous,ring-cell carcinomas,etc.),analysis of mechanisms of carcinogenesis involved(chromosomal instability,microsatellite instability,CpG island methylator phenotype)and mutational statuses of commonly altered genes(KRAS,NRAS,BRAF,APC,etc.),as well as expression signatures(CMS 1-4).It is also suggested that the tumor microenvironment is a key player in tumor progression and metastasis in CRC.According to the latest data,the immune microenvironment can also be predictive of the response to immune checkpoint inhibitors.In this review,we highlight how the immune environment influences CRC prognosis and sensitivity to systemic therapy.展开更多
Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon c...Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon cancer are diagnosed at an early stage(stages I to III),which provides an opportunity for cure.The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients,which is directed at the eradication of minimal residual disease to achieve a cure.Surgery alone is curative for the vast majority of colon cancer patients.Currently,surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement.Adjuvant chemotherapy is recommended for all patients with stage III colon cancer,while the benefit in stage II patients is not unequivocally established despite several large clinical trials.Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques,strategies to limit treatment-related toxicities,precise patient selection for adjuvant therapy,utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology.In this review,we will discuss the current standard treatment,evolving treatment paradigms,and the emerging biomarkers,that will likely help improve patient selection and personalization of therapy leading to superior outcomes.展开更多
Objective:The immunoscore,which is used to quantify immune infiltrates,has greater relative prognostic value than tumor,node,and metastasis(TNM)stage and might serve as a new system for classification of colorectal ca...Objective:The immunoscore,which is used to quantify immune infiltrates,has greater relative prognostic value than tumor,node,and metastasis(TNM)stage and might serve as a new system for classification of colorectal cancer.However,a comparable immunoscore for predicting lung adenocarcinoma(LUAD)prognosis is currently lacking.Methods:We analyzed the expression of 18 immune features by immunohistochemistry in 171 specimens.The relationship of immune marker expression and clinicopathologic factors to the overall survival(OS)was analyzed with the Kaplan-Meier method.A nomogram was developed by using the optimal features selected by least absolute shrinkage and selection operator(LASSO)regression in the training cohort(n=111)and evaluated in the validation cohort(n=60).Results:The indicators integrated in the nomogram were TNM stage,neuron-specific enolase,carcino-embryonic antigen,CD8 center of tumor(CT),CD8 invasive margin(IM),Fox P3 CT,and CD45 ROCT.The calibration curve showed prominent agreement between the observed 2-and 5-year OS and that predicted by the nomogram.To simplify the nomogram,we developed a new immune-serum scoring system(I-SSS)based on the points awarded for each factor in the nomogram.Our I-SSS was able to stratify same-stage patients into different risk subgroups.The combination of I-SSS and TNM stage had better prognostic value than the TNM stage alone.Conclusions:Our new I-SSS can accurately and individually predict LUAD prognosis and may be used to supplement prognostication based on the TNM stage.展开更多
Following initial success in melanoma and lung tumours,immune checkpoint inhibitors(ICIs)are now well recognized as a major immunotherapy treatment modality for multiple types of solid cancers.In colorectal cancer(CRC...Following initial success in melanoma and lung tumours,immune checkpoint inhibitors(ICIs)are now well recognized as a major immunotherapy treatment modality for multiple types of solid cancers.In colorectal cancer(CRC),the small subset that is mismatch-repair-deficient and microsatellite-instability-high(dMMR/MSI-H)derive benefit from immunotherapy;however,the vast majority of patients with proficient MMR(pMMR)or with microsatellite stable(MSS)CRC do not.Immunoscore and the consensus molecular subtype classifications are promising biomarkers in predicting therapeutic efficacy in selected CRC.In pMRR/MSS CRC,biomarkers are also needed to understand the molecular mechanisms governing immune reactivity and to predict their relationship to treatment.The continuous development of such biomarkers would offer new perspectives and more personalized treatments by targeting oncological options,including ICIs,which modify the tumour-immune microenvironment.In this review,we focus on CRC and discuss the current status of ICIs,the role of biomarkers to predict response to immunotherapy,and the approaches being explored to render pMMR/MSS CRC more immunogenic through the use of combined therapies.展开更多
基金supported by the National Key Research and Development Program of China(No.2017YFC1309102)National Natural Science Foundation of China(No.81771912,No.82001986,No.82071892)+1 种基金National Science Fund for Distinguished Young Scholars(No.81925023)High-level Hospital Construction Project(No.DFJH201805 and No.DFJH201914)。
文摘Objective: The Immunoscore method has proved fruitful for predicting prognosis in patients with colon cancer.However, there is still room for improvement in this scoring method to achieve further advances in its clinical translation. This study aimed to develop and validate a modified Immunoscore(IS-mod) system for predicting overall survival(OS) in patients with stage Ⅰ-Ⅲ colon cancer.Methods: The IS-mod was proposed by counting CD3+ and CD8+ immune cells in regions of the tumor core and its invasive margin by drawing two lines of interest. A discovery cohort(N=212) and validation cohort(N=103)from two centers were used to evaluate the prognostic value of the IS-mod.Results: In the discovery cohort, 5-year survival rates were 88.6% in the high IS-mod group and 60.7% in the low IS-mod group. Multivariate analysis confirmed that the IS-mod was an independent prognostic factor for OS[adjusted hazard ratio(HR)=0.36, 95% confidence interval(95% CI): 0.20-0.63]. With less annotation and computation cost, the IS-mod achieved performance comparable to that of the Immunoscore-like(IS-like) system(C-index, 0.676 vs. 0.661, P=0.231). The 2-category IS-mod using 47.5% as the threshold had a better prognostic value than that using a fixed threshold of 25%(C-index, 0.653 vs. 0.573, P=0.004). Similar results were confirmed in the validation cohort.Conclusions: Our method simplifies the annotation and accelerates the calculation of Immunoscore method,thus making it easier for clinical implementation. The IS-mod achieved comparable prognostic performance when compared to the IS-like system in both cohorts. Besides, we further found that even with a small reference set(N≥120), the IS-mod still demonstrated a stable prognostic value. This finding may inspire other institutions to develop a local reference set of an IS-mod system for more accurate risk stratification of colon cancer.
文摘Objective:Pretreatment prediction of Immunoscore in patients with hepatocellular cancer(HCC)is important for precision immunotherapy.We aimed to develop a radiomics model based on gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid(Gd-EOB-DTPA)-enhanced magnetic resonance imaging(MRI)for pretreatment prediction of Immunoscore(0-2 vs.3-4)in HCC.
基金Xunta de Galicia(Ayudas de Consolidación y Estructuración de Unidades de Investigación Competitivas de la Consellería de Cultura,Educación,Formación Profesional y Universidades,GRC,ED431C 2023/28 and GRC,ED431C 2023/09).
文摘In this editorial we comment on the article by Agatsuma et al published in the World Journal of Gastroenterology.They suggest policies for more effective colorectal screening.Screening is the main policy that has led to lower mortality rates in later years among the population that was eligible for screening.Colonoscopy is the gold standard tool for screening and has preventive effects by removing precancerous or early malignant polyps.However,colonoscopy is an invasive process,and fecal tests such as the current hemoglobin immunodetection were developed,followed by endoscopy,as the general tool for population screening,avoiding logistical and economic problems.Even so,participation and adherence rates are low.Different screening options are being developed with the idea that if people could choose between the ones that best suit them,participation in population-based screening programs would increase.Blood tests,such as a recent one that detects cell-free DNA shed by tumors called circulating tumor DNA,showed a similar accuracy rate to stool tests for cancer,but were less sensitive for advanced precancerous lesions.At the time when the crosstalk between the immune system and cancer was being established as a new hallmark of cancer,novel immune system-related biomarkers and information on patients’immune parameters,such as cell counts of different immune populations,were studied for the early detection of colorectal cancer,since they could be effective in asymptomatic people,appearing earlier in the adenoma-carcinoma development compared to the presence of fecal blood.sCD26,for example,detected 80.37%of advanced adenomas.To reach as many eligible people as possible,starting at an earlier age than current programs,the direction could be to apply tests based on blood,urine or salivary fluid to samples taken during routine visits to the primary health system.
文摘Colorectal cancer(CRC)represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death worldwide.The traditional classification of CRC is based on pathomorphological and molecular character-istics of tumor cells(mucinous,ring-cell carcinomas,etc.),analysis of mechanisms of carcinogenesis involved(chromosomal instability,microsatellite instability,CpG island methylator phenotype)and mutational statuses of commonly altered genes(KRAS,NRAS,BRAF,APC,etc.),as well as expression signatures(CMS 1-4).It is also suggested that the tumor microenvironment is a key player in tumor progression and metastasis in CRC.According to the latest data,the immune microenvironment can also be predictive of the response to immune checkpoint inhibitors.In this review,we highlight how the immune environment influences CRC prognosis and sensitivity to systemic therapy.
文摘Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies.The majority of patients with colon cancer are diagnosed at an early stage(stages I to III),which provides an opportunity for cure.The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients,which is directed at the eradication of minimal residual disease to achieve a cure.Surgery alone is curative for the vast majority of colon cancer patients.Currently,surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement.Adjuvant chemotherapy is recommended for all patients with stage III colon cancer,while the benefit in stage II patients is not unequivocally established despite several large clinical trials.Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques,strategies to limit treatment-related toxicities,precise patient selection for adjuvant therapy,utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology.In this review,we will discuss the current standard treatment,evolving treatment paradigms,and the emerging biomarkers,that will likely help improve patient selection and personalization of therapy leading to superior outcomes.
基金supported by the Tianjin Municipal Health Bureau Science and Technology Foundation(Grant No.16KG125)the Project of the National Natural Science Foundation of China(Grant No.81801781)the Project of Tumor Translational Medicine Seed Fund of the Tianjin Medical University Cancer Institute and Hospital(Grant No.1905)。
文摘Objective:The immunoscore,which is used to quantify immune infiltrates,has greater relative prognostic value than tumor,node,and metastasis(TNM)stage and might serve as a new system for classification of colorectal cancer.However,a comparable immunoscore for predicting lung adenocarcinoma(LUAD)prognosis is currently lacking.Methods:We analyzed the expression of 18 immune features by immunohistochemistry in 171 specimens.The relationship of immune marker expression and clinicopathologic factors to the overall survival(OS)was analyzed with the Kaplan-Meier method.A nomogram was developed by using the optimal features selected by least absolute shrinkage and selection operator(LASSO)regression in the training cohort(n=111)and evaluated in the validation cohort(n=60).Results:The indicators integrated in the nomogram were TNM stage,neuron-specific enolase,carcino-embryonic antigen,CD8 center of tumor(CT),CD8 invasive margin(IM),Fox P3 CT,and CD45 ROCT.The calibration curve showed prominent agreement between the observed 2-and 5-year OS and that predicted by the nomogram.To simplify the nomogram,we developed a new immune-serum scoring system(I-SSS)based on the points awarded for each factor in the nomogram.Our I-SSS was able to stratify same-stage patients into different risk subgroups.The combination of I-SSS and TNM stage had better prognostic value than the TNM stage alone.Conclusions:Our new I-SSS can accurately and individually predict LUAD prognosis and may be used to supplement prognostication based on the TNM stage.
基金N.H.is a research fellow supported by a grant from the Belgian National Fund for Scientific Research[Te´le´vie/FNRS 7460918F].
文摘Following initial success in melanoma and lung tumours,immune checkpoint inhibitors(ICIs)are now well recognized as a major immunotherapy treatment modality for multiple types of solid cancers.In colorectal cancer(CRC),the small subset that is mismatch-repair-deficient and microsatellite-instability-high(dMMR/MSI-H)derive benefit from immunotherapy;however,the vast majority of patients with proficient MMR(pMMR)or with microsatellite stable(MSS)CRC do not.Immunoscore and the consensus molecular subtype classifications are promising biomarkers in predicting therapeutic efficacy in selected CRC.In pMRR/MSS CRC,biomarkers are also needed to understand the molecular mechanisms governing immune reactivity and to predict their relationship to treatment.The continuous development of such biomarkers would offer new perspectives and more personalized treatments by targeting oncological options,including ICIs,which modify the tumour-immune microenvironment.In this review,we focus on CRC and discuss the current status of ICIs,the role of biomarkers to predict response to immunotherapy,and the approaches being explored to render pMMR/MSS CRC more immunogenic through the use of combined therapies.
