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Article ; Online: The age of enlightenment in melanoma immunotherapy.

Albertini, Mark R

2018 Volume 6, Issue 1, Page(s) 80

Abstract: An updated survival analysis by Callahan et al. published in the February 1, 2018 issue of the Journal of Clinical Oncology reported a 3-year overall survival (OS) rate of 63% for 94 patients with previously treated or untreated advanced melanoma who ... ...

Abstract	An updated survival analysis by Callahan et al. published in the February 1, 2018 issue of the Journal of Clinical Oncology reported a 3-year overall survival (OS) rate of 63% for 94 patients with previously treated or untreated advanced melanoma who received ipilimumab and nivolumab as concurrent therapy in a phase 1 dose escalation study CA209-004 (n = 53) or in an expansion cohort with the dose and schedule of concurrent ipilimumab and nivolumab now approved for patients with unresectable or metastatic melanoma (n = 41). While this 3-year OS rate of 63% in patients with measurable, unresectable stage III or IV melanoma is an impressive accomplishment that compares very favorably with historical metastatic melanoma survival rates, findings from larger phase 3 studies are needed to determine whether combination immunotherapy significantly improves survival more than single agent immunotherapy with PD-1 blockade. This Commentary discusses the transition from the dark ages to the age of enlightenment in melanoma immunotherapy and provides a roadmap for a better tomorrow for patients with metastatic melanoma.
MeSH term(s)	Antibodies, Monoclonal ; Humans ; Immunotherapy ; Ipilimumab ; Melanoma ; Nivolumab
Chemical Substances	Antibodies, Monoclonal ; Ipilimumab ; Nivolumab (31YO63LBSN)
Language	English
Publishing date	2018-08-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1186/s40425-018-0397-8
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Article: SURROGATE SELECTION OVERSAMPLES EXPANDED T CELL CLONOTYPES.

Yu, Peng / Lian, Yumin / Zuleger, Cindy L / Albertini, Richard J / Albertini, Mark R / Newton, Michael A

bioRxiv : the preprint server for biology

2023

Abstract: Inference from immunological data on cells in the adaptive immune system may benefit from modeling specifications that describe variation in the sizes of various clonal sub-populations. We develop one such specification in order to quantify the effects ... ...

Abstract	Inference from immunological data on cells in the adaptive immune system may benefit from modeling specifications that describe variation in the sizes of various clonal sub-populations. We develop one such specification in order to quantify the effects of surrogate selection assays, which we confirm may lead to an enrichment for amplified, potentially disease-relevant
Language	English
Publishing date	2023-07-15
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.13.548950
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Article ; Online: Development of a next-generation sequencing protocol for the canine T cell receptor beta chain repertoire.

Zuleger, Cindy L / Schwartz, Rene Welch / Ong, Irene M / Newton, Michael A / Vail, David M / Albertini, Mark R

Veterinary immunology and immunopathology

2023 Volume 268, Page(s) 110702

Abstract: Profiling the T cell receptor (TCR) repertoire using next-generation sequencing has become common in both human and translational research. Companion dogs with spontaneous tumors, including canine melanoma, share several features, e.g., natural ... ...

Abstract	Profiling the T cell receptor (TCR) repertoire using next-generation sequencing has become common in both human and translational research. Companion dogs with spontaneous tumors, including canine melanoma, share several features, e.g., natural occurrence, shared environmental exposures, natural outbred population, and immunocompetence. T cells play an important role in the adaptive immune system by recognizing specific antigens via a surface TCR. As such, understanding the canine T cell response to vaccines, cancer, immunotherapies, and infectious diseases is critically important for both dog and human health. Off-the-shelf commercial reagents, kits and services are readily available for human, non-human primate, and mouse in this context. However, these resources are limited for the canine. In this study, we present a cost-effective protocol for analysis of canine TCR beta chain genes. Workflow can be accomplished in 1-2 days starting with total RNA and resulting in libraries ready for sequencing on Illumina platforms.
MeSH term(s)	Dogs ; Animals ; Mice ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; T-Lymphocytes ; High-Throughput Nucleotide Sequencing/veterinary
Chemical Substances	Receptors, Antigen, T-Cell, alpha-beta
Language	English
Publishing date	2023-12-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2023.110702
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Zs.A 2177: Show issues

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Article ; Online: Neutrophil-to-eosinophil ratio as a biomarker for clinical outcomes in advanced stage melanoma patients treated with anti-PD-1 therapy.

Pozorski, Vincent / Park, Yeonhee / Mohamoud, Yusuf / Tesfamichael, Dahlia / Emamekhoo, Hamid / Birbrair, Alexander / Albertini, Mark R / Ma, Vincent T

Pigment cell & melanoma research

2023 Volume 36, Issue 6, Page(s) 501–511

Abstract: Neutrophil-to-lymphocyte ratios (NLR) and eosinophil counts are associated with improved survival in melanoma patients treated with immune checkpoint inhibitors, but no study has investigated neutrophil-to-eosinophil ratios (NER) as a predictive ... ...

Abstract	Neutrophil-to-lymphocyte ratios (NLR) and eosinophil counts are associated with improved survival in melanoma patients treated with immune checkpoint inhibitors, but no study has investigated neutrophil-to-eosinophil ratios (NER) as a predictive indicator in this population. In this retrospective study evaluating anti-PD-1 treated patients with advanced melanoma, progression-free survival (PFS), overall survival (OS), objective response rates (ORR), and risk of high-grade (grade ≥3) immune-related adverse events (irAEs) were compared between groups defined by median pretreatment NLR and NER as well as median NLR and NER at 1-month post-treatment. Lower baseline NLR and NER were associated with improved OS [HR: 0.504, 95% CI: 0.328-0.773, p = .002 and HR: 0.442, 95% CI: 0.288-0.681, p < .001, respectively] on univariate testing. After accounting for multiple covariates, our multivariate analysis found that lower pretreatment NER was associated with better ORR (by irRECIST) (OR: 2.199, 95% CI: 1.071-4.582, p = .033) and improved OS (HR: 0.480, 95% CI: 0.296-0.777, p = .003). Baseline NLR, 1-month NLR, and 1-month NER were not associated with ORR, PFS, or OS outcomes; but 1-month NER correlated with lower risk of grade ≥3 irAEs (OR: 0.392, 95% CI: 0.165-0.895, p = .029). Our findings suggest baseline NER merits additional investigation as a novel prognostic marker for advanced melanoma patients receiving anti-PD-1-based regimens.
MeSH term(s)	Humans ; Neutrophils ; Eosinophils ; Retrospective Studies ; Treatment Outcome ; Melanoma ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-07-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2409570-9
ISSN	1755-148X ; 1600-0749 ; 0893-5785 ; 1755-1471
ISSN (online)	1755-148X ; 1600-0749
ISSN	0893-5785 ; 1755-1471
DOI	10.1111/pcmr.13109
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Zs.A 2444: Show issues

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Article ; Online: FDG PET/CT for Assessment of Immune Therapy: Opportunities and Understanding Pitfalls.

Cho, Steve Y / Huff, Daniel T / Jeraj, Robert / Albertini, Mark R

Seminars in nuclear medicine

2020 Volume 50, Issue 6, Page(s) 518–531

Abstract: Immune checkpoint blockade has demonstrated the ability to modulate the immune system to produce durable responses in a wide range of cancers and has significantly impacted the standard of care. However, many cancer patients still do not respond to ... ...

Abstract	Immune checkpoint blockade has demonstrated the ability to modulate the immune system to produce durable responses in a wide range of cancers and has significantly impacted the standard of care. However, many cancer patients still do not respond to immune checkpoint blockade or have a limited duration of antitumor responses. Moreover, immune-related adverse events caused by immune checkpoint blockade can be severe and debilitating for some patients, limiting continuation of therapy and resulting in severe autoimmune conditions. Standard-of-care conventional anatomic imaging modalities and tumor response criteria have limitations to adequately assess tumor responses, especially early in the course of therapy, for risk-adapted clinical management to inform care of patients treated with immunotherapy. Molecular imaging with position emission tomography (PET) provides a noninvasive functional biomarker of tumor response, and of immune activation, for patients on immune-based therapies to help address these needs.
MeSH term(s)	Fluorodeoxyglucose F18 ; Humans ; Immunotherapy ; Neoplasms/diagnostic imaging ; Neoplasms/immunology ; Neoplasms/therapy ; Positron Emission Tomography Computed Tomography ; Prognosis
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2020-06-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	120248-0
ISSN	1558-4623 ; 0001-2998
ISSN (online)	1558-4623
ISSN	0001-2998
DOI	10.1053/j.semnuclmed.2020.06.001
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Zs.A 763: Show issues

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Article: Retrograde Balloon-Assisted Deep Enteroscopy in the Diagnosis of Metastatic Melanoma.

Barge, William / Albertini, Mark R / Cold, Christopher / Abbott, Daniel / Gopal, Deepak

Case reports in gastrointestinal medicine

2021 Volume 2021, Page(s) 5572230

Abstract: A 74-year-old male with a history of metastatic melanoma presents with persistently abnormal small bowel findings on PET-CT scan. The patient had persistent FDG uptake near the ileocolic junction on imaging, concerning for metastatic melanoma. Capsule ... ...

Abstract	A 74-year-old male with a history of metastatic melanoma presents with persistently abnormal small bowel findings on PET-CT scan. The patient had persistent FDG uptake near the ileocolic junction on imaging, concerning for metastatic melanoma. Capsule endoscopy demonstrated ulcerated mucosa in the distal ileum. This area was biopsied and tattooed via retrograde double-balloon enteroscopy to confirm the diagnosis of metastatic melanoma and facilitate subsequent small bowel resection. The case illustrates a unique case of metastatic melanoma to the small bowel and the utility of capsule endoscopy and balloon-assisted enteroscopy to assist in diagnosis and management of metastatic disease.
Language	English
Publishing date	2021-06-30
Publishing country	United States
Document type	Case Reports
ZDB-ID	2627636-7
ISSN	2090-6536 ; 2090-6528
ISSN (online)	2090-6536
ISSN	2090-6528
DOI	10.1155/2021/5572230
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Article ; Online: Molecular characterization of hypoxanthine guanine phosphoribosyltransferase mutant T cells in human blood: The concept of surrogate selection for immunologically relevant cells.

Kaitz, Noah A / Zuleger, Cindy L / Yu, Peng / Newton, Michael A / Albertini, Richard J / Albertini, Mark R

Mutation research. Reviews in mutation research

2022 Volume 789, Page(s) 108414

Abstract: Somatic cell gene mutations arise in vivo due to replication errors during DNA synthesis occurring spontaneously during normal DNA synthesis or as a result of replication on a DNA template damaged by endogenous or exogenous mutagens. In principle, ... ...

Abstract	Somatic cell gene mutations arise in vivo due to replication errors during DNA synthesis occurring spontaneously during normal DNA synthesis or as a result of replication on a DNA template damaged by endogenous or exogenous mutagens. In principle, changes in the frequencies of mutant cells in vivo in humans reflect changes in exposures to exogenous or endogenous DNA damaging insults, other factors being equal. It is becoming increasingly evident however, that somatic mutations in humans have a far greater range of interpretations. For example, mutations in lymphocytes provide invaluable probes for in vivo cellular and molecular processes, providing identification of clonal amplifications of these cells in autoimmune and infectious diseases, transplantation recipients, paroxysmal nocturnal hemoglobinuria (PNH), and cancer. The assay for mutations of the X-chromosomal hypoxanthine guanine phosphoribosyltransferase (HPRT) gene has gained popular acceptance for this purpose since viable mutant cells can be recovered for molecular and other analyses. Although the major application of the HPRT T cell assay remains human population monitoring, the enrichment of activated T cells in the mutant fraction in individuals with ongoing immunological processes has demonstrated the utility of surrogate selection, a method that uses somatic mutation as a surrogate marker for the in vivo T cell proliferation that underlies immunological processes to investigate clinical disorders with immunological features. Studies encompassing a wide range of clinical conditions are reviewed. Despite the historical importance of the HPRT mutation system in validating surrogate selection, there are now additional mutational and other methods for identifying immunologically active T cells. These methods are reviewed and provide insights for strategies to extend surrogate selection in future studies.
MeSH term(s)	DNA ; Humans ; Hypoxanthine Phosphoribosyltransferase/genetics ; Hypoxanthine Phosphoribosyltransferase/pharmacology ; Mutagens/pharmacology ; Mutation ; T-Lymphocytes
Chemical Substances	Mutagens ; DNA (9007-49-2) ; Hypoxanthine Phosphoribosyltransferase (EC 2.4.2.8)
Language	English
Publishing date	2022-03-11
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2727833-5
ISSN	1388-2139 ; 1383-5742
ISSN (online)	1388-2139
ISSN	1383-5742
DOI	10.1016/j.mrrev.2022.108414
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Zs.A 1316 -Rev-: Show issues

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Article ; Online: Development and validation of a longitudinal soft-tissue metastatic lesion matching algorithm.

Santoro-Fernandes, Victor / Huff, Daniel / Scarpelli, Mathew L / Perk, Timothy G / Albertini, Mark R / Perlman, Scott / Yip, Stephen S F / Jeraj, Robert

Physics in medicine and biology

2021 Volume 66, Issue 15

Abstract: Metastatic cancer presents with many, sometimes hundreds of metastatic lesions through the body, which often respond heterogeneously to treatment. Therefore, lesion-level assessment is necessary for a complete understanding of disease response. Lesion- ... ...

Abstract	Metastatic cancer presents with many, sometimes hundreds of metastatic lesions through the body, which often respond heterogeneously to treatment. Therefore, lesion-level assessment is necessary for a complete understanding of disease response. Lesion-level assessment typically requires manual matching of corresponding lesions, which is a tedious, subjective, and error-prone task. This study introduces a fully automated algorithm for matching of metastatic lesions in longitudinal medical images. The algorithm entails four steps: (1) image registration, (2) lesion dilation, (3) lesion clustering, and (4) linear assignment. In step (1), 3D deformable registration is used to register the scans. In step (2), lesion contours are conformally dilated. In step (3), lesion clustering is evaluated based on local metrics. In step (4), matching is assigned based on non-greedy cost minimization. The algorithm was optimized (e.g. choice of deformable registration algorithm, dilatation size) and validated on 140 scan-pairs of 32 metastatic cancer patients from two independent clinical trials, who received longitudinal PET/CT scans as part of their treatment response assessment. Registration error was evaluated using landmark distance. A sensitivity study was performed to evaluate the optimal lesion dilation magnitude. Lesion matching performance accuracy was evaluated for all patients and for a subset with high disease burden. Two investigated deformable registration approaches (whole body deformable and articulated deformable registrations) led to similar performance with the overall registration accuracy between 2.3 and 2.6 mm. The optimal dilation magnitude of 25 mm yielded almost a perfect matching accuracy of 0.98. No significant matching accuracy decrease was observed in the subset of patients with high lesion disease burden. In summary, lesion matching using our new algorithm was highly accurate and a significant improvement, when compared to previously established methods. The proposed method enables accurate automated metastatic lesion matching in whole-body longitudinal scans.
MeSH term(s)	Algorithms ; Humans ; Image Processing, Computer-Assisted ; Neoplasms ; Positron Emission Tomography Computed Tomography ; Tomography, X-Ray Computed
Language	English
Publishing date	2021-07-30
Publishing country	England
Document type	Journal Article
ZDB-ID	208857-5
ISSN	1361-6560 ; 0031-9155
ISSN (online)	1361-6560
ISSN	0031-9155
DOI	10.1088/1361-6560/ac1457
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Zs.A 199: Show issues

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Article ; Online: Enrichment of melanoma-associated T cells in 6-thioguanine-resistant T cells from metastatic melanoma patients.

Zuleger, Cindy L / Newton, Michael A / Ma, Xiuyu / Ong, Irene M / Pei, Qinglin / Albertini, Mark R

Melanoma research

2019 Volume 30, Issue 1, Page(s) 52–61

Abstract: This study examines whether 6-thioguanine resistant T cells (mutant) from metastatic melanoma patients are enriched for melanoma-associated T cells compared to T cells obtained analogously without thioguanine selection (wild-type). Melanoma-associated ... ...

Abstract	This study examines whether 6-thioguanine resistant T cells (mutant) from metastatic melanoma patients are enriched for melanoma-associated T cells compared to T cells obtained analogously without thioguanine selection (wild-type). Melanoma-associated antigen pentamer staining was performed on 5 tumour and 9 peripheral blood samples from metastatic melanoma patients. T cell receptor beta chain repertoire was examined via Sanger sequencing of mutant and wild-type in blood and tumour from metastatic melanoma patients at times of tumour progression (n = 8) and via Illumina sequencing in tumour derived T cells and in uncultured T cells (uncultured), wild-type and mutant from blood before and after immune checkpoint blockade (n = 1). Mutant from tumour (3 of 5; P < 0.001), but not blood (0 of 9), were enriched compared to wild-type for binding melanoma-associated antigen pentamers. T cell receptor beta analysis in patients with tumour progression (n = 8) detected increased melanoma associated T cells in mutant compared to wild-type from blood (Monte Carlo P = 10). Comparison of blood samples before and after immune checkpoint blockade with prior tumor from one metastatic melanoma patient detected increased T cell receptor beta sharing between tumour and mutant compared to tumour and wild-type or tumour and uncultured: 11.0% (72/656), 1.5% (206/13 639) and 1.3% (381/29 807), respectively (Monte Carlo P = 10 for mutant versus wild-type and mutant versus uncultured). These data demonstrate that mutant in metastatic melanoma patients are enriched for melanoma-associated T cells and are candidate probes to study in vivo melanoma-reactive T cells.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Humans ; Melanoma/immunology ; Middle Aged ; T-Lymphocytes/immunology
Language	English
Publishing date	2019-06-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1095779-0
ISSN	1473-5636 ; 0960-8931
ISSN (online)	1473-5636
ISSN	0960-8931
DOI	10.1097/CMR.0000000000000625
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Zs.A 3378: Show issues

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Article ; Online: OMIP-008: measurement of Th1 and Th2 cytokine polyfunctionality of human T cells.

Zuleger, Cindy L / Albertini, Mark R

Cytometry. Part A : the journal of the International Society for Analytical Cytology

2012 Volume 81, Issue 6, Page(s) 450–452

MeSH term(s)	Antigens, Neoplasm/immunology ; Blood Cells/cytology ; Blood Cells/immunology ; CD8-Positive T-Lymphocytes ; Case-Control Studies ; Cryopreservation ; Cytokines/analysis ; Cytokines/immunology ; Flow Cytometry ; Fluorescent Dyes ; Humans ; Immunophenotyping ; Lymphocyte Activation/immunology ; Melanoma/immunology ; Melanoma/metabolism ; Melanoma/pathology ; Primary Cell Culture ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Th1 Cells/pathology ; Th1-Th2 Balance ; Th2 Cells/immunology ; Th2 Cells/metabolism ; Th2 Cells/pathology ; Tumor Microenvironment/immunology
Chemical Substances	Antigens, Neoplasm ; Cytokines ; Fluorescent Dyes
Language	English
Publishing date	2012-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2099868-5
ISSN	1552-4930 ; 0196-4763 ; 1552-4922
ISSN (online)	1552-4930
ISSN	0196-4763 ; 1552-4922
DOI	10.1002/cyto.a.22035
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