Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic setting.ChRCCs are considered to originate from the intercalated cell of distal t...Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic setting.ChRCCs are considered to originate from the intercalated cell of distal tubules with two main morphological variants,classic and eosinophilic.Most ChRCCs carry a favorable clinical outcome.Histology alone is limited in predicting the behavior of ChRCCs that do not have overtly aggressive morphologic findings such as necrosis and sarcomatoid features.Along with positive CD117 expression,classic ChRCCs generally express diffuse and uniform CK7,while eosinophilic variant demonstrates more heterogeneous CK7 expression(rare or patchy).Multiple losses of chromosomes 1,2,6,10,13,17,and 21 are considered to be the genetic hallmarks of classic and eosinophilic ChRCCs,while chromosomal gains are known to be associated with sarcomatoid ChRCCs.TP53 and PTEN are the two most frequently mutated genes in ChRCCs.The major challenge in the differential diagnosis of ChRCCs includes considerations around the eosinophilic variant(of ChRCCs),where it may share overlapping features with oncocytoma or other recent emergent oncocytic tumors.Most eosinophilic ChRCCs share expression of the recently described biomarkers,LINC01187 and FOXI1,with classic ChRCCs,however,a subset of eosinophilic-like ChRCCs with lower biomarker expression have been demonstrated to harbor MTOR gene mutations.Overall,the morphologic features of ChRCCs and genetic profile with combinations of chromosomal losses and gains suggest this tumor entity to represent a distinct,yet heterogeneous group of renal neoplasms.展开更多
Objective.Seven types of MRI artifacts,including acquisition and preprocessing errors,were simulated to test a machine learning brain tumor segmentation model for potential failure modes.Introduction.Real-world medica...Objective.Seven types of MRI artifacts,including acquisition and preprocessing errors,were simulated to test a machine learning brain tumor segmentation model for potential failure modes.Introduction.Real-world medical deployments of machine learning algorithms are less common than the number of medical research papers using machine learning.Part of the gap between the performance of models in research and deployment comes from a lack of hard test cases in the data used to train a model.Methods.These failure modes were simulated for a pretrained brain tumor segmentation model that utilizes standard MRI and used to evaluate the performance of the model under duress.These simulated MRI artifacts consisted of motion,susceptibility induced signal loss,aliasing,field inhomogeneity,sequence mislabeling,sequence misalignment,and skull stripping failures.Results.The artifact with the largest effect was the simplest,sequence mislabeling,though motion,field inhomogeneity,and sequence misalignment also caused significant performance decreases.The model was most susceptible to artifacts affecting the FLAIR(fluid attenuation inversion recovery)sequence.Conclusion.Overall,these simulated artifacts could be used to test other brain MRI models,but this approach could be used across medical imaging applications.展开更多
The majority of colorectal cancer patients are not responsive to immune checkpoint blockade(ICB).The interferon gamma(IFNγ)signaling pathway drives spontaneous and ICB-induced antitumor immunity.In this review,we sum...The majority of colorectal cancer patients are not responsive to immune checkpoint blockade(ICB).The interferon gamma(IFNγ)signaling pathway drives spontaneous and ICB-induced antitumor immunity.In this review,we summarize recent advances in the epigenetic,genetic,and functional integrity of the IFNγsignaling pathway in the colorectal cancer microenvironment and its immunological relevance in the therapeutic efficacy of and resistance to ICB.Moreover,we discuss how to target IFNγsignaling to inform novel clinical trials to treat patients with colorectal cancer.展开更多
Cancer immunotherapy,including immune checkpoint blockade and CAR-T cell therapy,has introduced revolutionary approaches to treating patients with cancer.The success and hope of cancer immunotherapy have continuously ...Cancer immunotherapy,including immune checkpoint blockade and CAR-T cell therapy,has introduced revolutionary approaches to treating patients with cancer.The success and hope of cancer immunotherapy have continuously stimulated high interest in dissecting immunotherapy resistance mechanisms,researching previously unknown therapeutic targets,and informing novel clinical trials in cancer therapy.The notion that the tumor microenvironment holds the key to understanding tumor immunity and developing novel immunotherapy has been well established in the field of tumor immunology and medical oncology[1].This special issue of Cellular&Molecular Immunology(CMI)compiles a series of review articles,presenting state-ofthe-art literature and concepts focused on several important aspects concerning the most recent advancement in immune sensitive and resistant mechanisms in the tumor microenvironment,and their relevance in cancer therapy.展开更多
Unresectable recurrent or metastatic head and neck cancer is an incurable disease with survival of approximately 12 months. Head and neck tumors exhibit numerous derangements in the tumor microenvironment that aid in ...Unresectable recurrent or metastatic head and neck cancer is an incurable disease with survival of approximately 12 months. Head and neck tumors exhibit numerous derangements in the tumor microenvironment that aid in immune evasion and may serve as targets for future therapies. Pembrolizumab is now approved as a first line therapy. Despite the promise of currently approved immunotherapies there continues to be low response rates and additional strategies are needed. Here, alterations in the immune microenvironment and current therapeutic strategies are reviewed with a focus on novel immunologic approaches.展开更多
The incidence of human papillomavirus(HPV)-related oropharyngeal squamous cell carcinoma(OPSCC)will continue to rise in the United States over the next several decades.Thus,efforts to reduce treatment intensity,mitiga...The incidence of human papillomavirus(HPV)-related oropharyngeal squamous cell carcinoma(OPSCC)will continue to rise in the United States over the next several decades.Thus,efforts to reduce treatment intensity,mitigate long-term physical and psychological sequelae of treatment,and simplify surveillance regimens for patients with HPV-related OPSCC are critical.Liquid biomarkers,namely plasma circulating tumor HPV DNA(ctDNA),have shown considerable promise for improvements in these domains by guiding personalized and adaptive treatment de-escalation paradigms and predicting disease recurrence in the survivorship period.Preliminary reports suggest an even broader impact of plasma HPV ctDNA assays for HPV-related OPSCC surveillance beyond the mere detection of cancer recurrence and metastasis.For instance,such assays may reduce the need for costly imaging studies,alleviate the financial toxicities of survivorship care,and improve care access and patient satisfaction.Currently,veterans and underserved populations are disproportionately affected by the financial burden of cancer surveillance and survivorship care.These disparities negatively impact oncologic outcomes,healthcare access,and utilization,specifically among veterans with HPV-related OPSCC.As such,we posit that HPV ctDNA monitoring may be of unique benefit and impact in the surveillance period for these patients specifically.Herein,we provide a narrative review of the current literature supporting the formal clinical evaluation of HPV ctDNA monitoring in veterans with HPV-related OPSCC.展开更多
While both the spleen and lymph nodes are called secondary lymphoid tissues,how lymphocytes enter these tissues are quite different from each other.This is because the architecture of the two types of organs and the m...While both the spleen and lymph nodes are called secondary lymphoid tissues,how lymphocytes enter these tissues are quite different from each other.This is because the architecture of the two types of organs and the mode of lymphocyte migration into these organs are quite distinct.In the spleen,T cells are passively released in the blood flow from the arterioles in the red pulp and marginal zone area.In contrast,T cells in the blood are actively captured on high endothelial venules in lymph nodes by the coordinated actions of CCR7 and several adhesion molecules.A recent finding indicates that T cells,released in the red pulp and marginal zone areas,actively find their way to the white zone by utilizing the migration track created by periarteriolar stromal cells.This finding adds one more piece to our understanding of lymphocyte migration for effective adaptive immune responses in the spleen.展开更多
Aim:To develop a comprehensive item library of patient-reported,immunotherapy-related adverse events(irAEs)that draws from and expands on the Functional Assessment of Chronic Illness Therapy(FACIT)Measurement System.M...Aim:To develop a comprehensive item library of patient-reported,immunotherapy-related adverse events(irAEs)that draws from and expands on the Functional Assessment of Chronic Illness Therapy(FACIT)Measurement System.Methods:Literature review and iterative expert input.Based on a literature review of irAEs,we developed a framework of immunotherapy classes and their associated symptoms.Clinical experts then reviewed iterations of symptom summaries and item maps linked to the immunotherapy framework.Experts provided content review and feedback was shared across experts until consensus was reached.The iterative process facilitated creation of a Primary Symptom List associated with immune checkpoint modulators(ICMs),drawn from the larger set of symptoms.Existing FACIT items were mapped to the symptom list,and new items were written as needed to create the item library.Results:The full item library of irAEs is comprised of 239 items,covering 142 unique symptoms across 75 inflammatory reactions/immune conditions.A subset of 66 items comprises a Primary Symptom List considered most common/relevant to ICM treatment.This includes gastrointestinal,skin,pulmonary,neurologic,musculoskeletal,and multiple miscellaneous and constitutional symptoms.Conclusion:The FACIT Immunotherapy Item Library is a compilation of 239 self-report items that capture the wide range of AEs experienced by people receiving immune treatments.A subset of 66 items comprises a Primary Symptom List meant for ICM therapy.Use of items selected from this library is encouraged in clinical research and clinical practice evaluation.展开更多
文摘Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic setting.ChRCCs are considered to originate from the intercalated cell of distal tubules with two main morphological variants,classic and eosinophilic.Most ChRCCs carry a favorable clinical outcome.Histology alone is limited in predicting the behavior of ChRCCs that do not have overtly aggressive morphologic findings such as necrosis and sarcomatoid features.Along with positive CD117 expression,classic ChRCCs generally express diffuse and uniform CK7,while eosinophilic variant demonstrates more heterogeneous CK7 expression(rare or patchy).Multiple losses of chromosomes 1,2,6,10,13,17,and 21 are considered to be the genetic hallmarks of classic and eosinophilic ChRCCs,while chromosomal gains are known to be associated with sarcomatoid ChRCCs.TP53 and PTEN are the two most frequently mutated genes in ChRCCs.The major challenge in the differential diagnosis of ChRCCs includes considerations around the eosinophilic variant(of ChRCCs),where it may share overlapping features with oncocytoma or other recent emergent oncocytic tumors.Most eosinophilic ChRCCs share expression of the recently described biomarkers,LINC01187 and FOXI1,with classic ChRCCs,however,a subset of eosinophilic-like ChRCCs with lower biomarker expression have been demonstrated to harbor MTOR gene mutations.Overall,the morphologic features of ChRCCs and genetic profile with combinations of chromosomal losses and gains suggest this tumor entity to represent a distinct,yet heterogeneous group of renal neoplasms.
基金supported by NIH grants R37CA214955-01A1CCSG Bioinformatics Shared Resource 5 P30 CA046592+2 种基金a Research Scholar Grant from the American Cancer Society (RSG-16-005-016,01)MIDAS/MICDE funding a Precision Health Investigator award from U-M Precision Health to A.R. (along with L.Rozek and M.Sartor)supported by The University of Michigan Ann Arbor (U-M)startup institutional research funds.
文摘Objective.Seven types of MRI artifacts,including acquisition and preprocessing errors,were simulated to test a machine learning brain tumor segmentation model for potential failure modes.Introduction.Real-world medical deployments of machine learning algorithms are less common than the number of medical research papers using machine learning.Part of the gap between the performance of models in research and deployment comes from a lack of hard test cases in the data used to train a model.Methods.These failure modes were simulated for a pretrained brain tumor segmentation model that utilizes standard MRI and used to evaluate the performance of the model under duress.These simulated MRI artifacts consisted of motion,susceptibility induced signal loss,aliasing,field inhomogeneity,sequence mislabeling,sequence misalignment,and skull stripping failures.Results.The artifact with the largest effect was the simplest,sequence mislabeling,though motion,field inhomogeneity,and sequence misalignment also caused significant performance decreases.The model was most susceptible to artifacts affecting the FLAIR(fluid attenuation inversion recovery)sequence.Conclusion.Overall,these simulated artifacts could be used to test other brain MRI models,but this approach could be used across medical imaging applications.
基金This work was supported in part by U.S.NIH/NCI R01 grants(CA217648,CA123088,CA099985,CA193136,CA152470)the NIH through the University of Michigan Rogel Cancer Center Grant(CA46592).
文摘The majority of colorectal cancer patients are not responsive to immune checkpoint blockade(ICB).The interferon gamma(IFNγ)signaling pathway drives spontaneous and ICB-induced antitumor immunity.In this review,we summarize recent advances in the epigenetic,genetic,and functional integrity of the IFNγsignaling pathway in the colorectal cancer microenvironment and its immunological relevance in the therapeutic efficacy of and resistance to ICB.Moreover,we discuss how to target IFNγsignaling to inform novel clinical trials to treat patients with colorectal cancer.
基金This work was supported in part by research grants from the NIH/NCI for WZ(CA248430,CA214911,CA123088,CA099985,CA193136,and CA152470)the NIH through the University of Michigan Rogel Cancer Center Support Grant(P30CA46592).
文摘Cancer immunotherapy,including immune checkpoint blockade and CAR-T cell therapy,has introduced revolutionary approaches to treating patients with cancer.The success and hope of cancer immunotherapy have continuously stimulated high interest in dissecting immunotherapy resistance mechanisms,researching previously unknown therapeutic targets,and informing novel clinical trials in cancer therapy.The notion that the tumor microenvironment holds the key to understanding tumor immunity and developing novel immunotherapy has been well established in the field of tumor immunology and medical oncology[1].This special issue of Cellular&Molecular Immunology(CMI)compiles a series of review articles,presenting state-ofthe-art literature and concepts focused on several important aspects concerning the most recent advancement in immune sensitive and resistant mechanisms in the tumor microenvironment,and their relevance in cancer therapy.
基金Heft Neal ME was supported in part by the NIH Grant(T32 DC005356).Brenner JC was supported in part by American Cancer Society Grant:132034-RSG-18-062-01-TBG.Brenner JC was supported by F31:DE-027600-01
文摘Unresectable recurrent or metastatic head and neck cancer is an incurable disease with survival of approximately 12 months. Head and neck tumors exhibit numerous derangements in the tumor microenvironment that aid in immune evasion and may serve as targets for future therapies. Pembrolizumab is now approved as a first line therapy. Despite the promise of currently approved immunotherapies there continues to be low response rates and additional strategies are needed. Here, alterations in the immune microenvironment and current therapeutic strategies are reviewed with a focus on novel immunologic approaches.
基金supported by a 2022 AHNS CORE Grant Presidential Award.
文摘The incidence of human papillomavirus(HPV)-related oropharyngeal squamous cell carcinoma(OPSCC)will continue to rise in the United States over the next several decades.Thus,efforts to reduce treatment intensity,mitigate long-term physical and psychological sequelae of treatment,and simplify surveillance regimens for patients with HPV-related OPSCC are critical.Liquid biomarkers,namely plasma circulating tumor HPV DNA(ctDNA),have shown considerable promise for improvements in these domains by guiding personalized and adaptive treatment de-escalation paradigms and predicting disease recurrence in the survivorship period.Preliminary reports suggest an even broader impact of plasma HPV ctDNA assays for HPV-related OPSCC surveillance beyond the mere detection of cancer recurrence and metastasis.For instance,such assays may reduce the need for costly imaging studies,alleviate the financial toxicities of survivorship care,and improve care access and patient satisfaction.Currently,veterans and underserved populations are disproportionately affected by the financial burden of cancer surveillance and survivorship care.These disparities negatively impact oncologic outcomes,healthcare access,and utilization,specifically among veterans with HPV-related OPSCC.As such,we posit that HPV ctDNA monitoring may be of unique benefit and impact in the surveillance period for these patients specifically.Herein,we provide a narrative review of the current literature supporting the formal clinical evaluation of HPV ctDNA monitoring in veterans with HPV-related OPSCC.
基金supported in part by grants from the NIH(R01AI121302 and R21AI14889801).
文摘While both the spleen and lymph nodes are called secondary lymphoid tissues,how lymphocytes enter these tissues are quite different from each other.This is because the architecture of the two types of organs and the mode of lymphocyte migration into these organs are quite distinct.In the spleen,T cells are passively released in the blood flow from the arterioles in the red pulp and marginal zone area.In contrast,T cells in the blood are actively captured on high endothelial venules in lymph nodes by the coordinated actions of CCR7 and several adhesion molecules.A recent finding indicates that T cells,released in the red pulp and marginal zone areas,actively find their way to the white zone by utilizing the migration track created by periarteriolar stromal cells.This finding adds one more piece to our understanding of lymphocyte migration for effective adaptive immune responses in the spleen.
基金Laurie E.Steffen McLouth was supported by NCI R25 CA122061(PI:Avis)Adam P.Dicker received additional support from the National Cancer Institute,the Prostate Cancer Research Program(Dept.of Defense)+1 种基金the American Society of Radiation Oncology,the American Society of Clinical Oncology,NRG Oncology,and the Prostate Cancer FoundationJosephine Feliciano received additional support from Bristol Myers Squibb and Astra Zeneca.
文摘Aim:To develop a comprehensive item library of patient-reported,immunotherapy-related adverse events(irAEs)that draws from and expands on the Functional Assessment of Chronic Illness Therapy(FACIT)Measurement System.Methods:Literature review and iterative expert input.Based on a literature review of irAEs,we developed a framework of immunotherapy classes and their associated symptoms.Clinical experts then reviewed iterations of symptom summaries and item maps linked to the immunotherapy framework.Experts provided content review and feedback was shared across experts until consensus was reached.The iterative process facilitated creation of a Primary Symptom List associated with immune checkpoint modulators(ICMs),drawn from the larger set of symptoms.Existing FACIT items were mapped to the symptom list,and new items were written as needed to create the item library.Results:The full item library of irAEs is comprised of 239 items,covering 142 unique symptoms across 75 inflammatory reactions/immune conditions.A subset of 66 items comprises a Primary Symptom List considered most common/relevant to ICM treatment.This includes gastrointestinal,skin,pulmonary,neurologic,musculoskeletal,and multiple miscellaneous and constitutional symptoms.Conclusion:The FACIT Immunotherapy Item Library is a compilation of 239 self-report items that capture the wide range of AEs experienced by people receiving immune treatments.A subset of 66 items comprises a Primary Symptom List meant for ICM therapy.Use of items selected from this library is encouraged in clinical research and clinical practice evaluation.
