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Article ; Online: Multimodal single-cell and whole-genome sequencing of small, frozen clinical specimens.

Wang, Yiping / Fan, Joy Linyue / Melms, Johannes C / Amin, Amit Dipak / Georgis, Yohanna / Barrera, Irving / Ho, Patricia / Tagore, Somnath / Abril-Rodríguez, Gabriel / He, Siyu / Jin, Yinuo / Biermann, Jana / Hofree, Matan / Caprio, Lindsay / Berhe, Simon / Khan, Shaheer A / Henick, Brian S / Ribas, Antoni / Macosko, Evan Z /

Chen, Fei / Taylor, Alison M / Schwartz, Gary K / Carvajal, Richard D / Azizi, Elham / Izar, Benjamin

Nature genetics

2023 Volume 55, Issue 1, Page(s) 19–25

Abstract: Single-cell genomics enables dissection of tumor heterogeneity and molecular underpinnings of drug response at an unprecedented ... ...

Abstract	Single-cell genomics enables dissection of tumor heterogeneity and molecular underpinnings of drug response at an unprecedented resolution
MeSH term(s)	Humans ; Genomics/methods ; Gene Expression Profiling/methods ; Neoplasms/genetics ; Sequence Analysis, RNA/methods ; Whole Genome Sequencing
Language	English
Publishing date	2023-01-09
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	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-022-01268-9
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Zs.MG 46: Show issues

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Article: Characterizing metastatic uveal melanoma patients who develop symptomatic brain metastases.

Wei, Alexander Z / Uriel, Matan / Porcu, Agata / Manos, Michael P / Mercurio, Ann C / Caplan, Michael M / Hulse, Liam / Seedor, Rino S / Holovatska, Marta / Francis, Jasmine / Khan, Shaheer A / McDonnell, Diana E / Bogomolny, Dmitry / Sato, Takami / Marr, Brian P / Haq, Rizwan / Orloff, Marlana / Shoushtari, Alexander / Carvajal, Richard D

Frontiers in oncology

2022 Volume 12, Page(s) 961517

Abstract: Metastatic uveal melanoma (mUM) is an advanced ocular malignancy characterized by a hepatotropic pattern of spread. As the incidence of brain metastases (BM) in mUM patients has been thought to be low, routine CNS surveillance has not been recommended. ... ...

Abstract	Metastatic uveal melanoma (mUM) is an advanced ocular malignancy characterized by a hepatotropic pattern of spread. As the incidence of brain metastases (BM) in mUM patients has been thought to be low, routine CNS surveillance has not been recommended. Notably, no formal assessment of BM incidence in mUM has to date been published to support this clinical practice. We aimed to determine the true rate of BM in mUM and to clarify the clinical and genomic risk factors associated with BM patients through a collaborative multicenter, retrospective research effort. Data collected from 1,845 mUM patients in databases across four NCI-designated comprehensive cancer centers from 2006-2021 were retrospectively analyzed to identify patients with BM. Brain imaging in most cases were performed due to onset of neurological symptoms and not for routine surveillance. An analysis of demographics, therapies, gene expression profile, tumor next generation sequencing (NGS) data, time to metastasis (brain or other), and survival in the BM cohort was completed. 116/1,845 (6.3%) mUM patients were identified with BM. The median age at time of UM diagnosis was 54 years old (range: 18-77). The median time to any metastasis was 4.2 years (range: 0-30.8). The most common initial metastatic site was the liver (75.9%). 15/116 (12.9%) BM patients presented with BM at the time of initial metastatic diagnosis. Median survival after a diagnosis of BM was 7.6 months (range: 0.4-73.9). The median number of organs involved at time of BM diagnosis was 3 (range: 1-9). DecisionDX-UM profiling was completed on 13 patients: 10-Class 2, 2-Class 1B, and 1-Class 1A. NGS and cytogenetic data were available for 34 and 21 patients, respectively. BM was identified in 6.3% of mUM cases and was associated with high disease burden and a median survival of under 8 months once diagnosed. Since most patients in this cohort were symptomatic, the incidence of asymptomatic BM remains unknown. These data suggest the use of routine brain imaging in all mUM patients at risk for developing BM for early detection.
Language	English
Publishing date	2022-09-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.961517
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Article ; Online: Concurrent radiotherapy and ipilimumab immunotherapy for patients with melanoma.

Barker, Christopher A / Postow, Michael A / Khan, Shaheer A / Beal, Kathryn / Parhar, Preeti K / Yamada, Yoshiya / Lee, Nancy Y / Wolchok, Jedd D

Cancer immunology research

2013 Volume 1, Issue 2, Page(s) 92–98

Abstract: Ipilimumab and radiotherapy are commonly used to treat unresectable and metastatic melanoma. Results from preclinical studies and case reports suggest a biologic interaction between these two treatments. To understand the clinical implications of the ... ...

Abstract	Ipilimumab and radiotherapy are commonly used to treat unresectable and metastatic melanoma. Results from preclinical studies and case reports suggest a biologic interaction between these two treatments. To understand the clinical implications of the interaction, we carried out a retrospective study reviewing records of patients treated with ipilimumab and radiotherapy for melanoma at our institution between 2005 and 2011. The review included details of treatment, response, adverse events (AE), and overall survival (OS). Twenty-nine patients underwent 33 courses of non-brain radiotherapy between their first and last dose of ipilimumab. Immune-related AEs (ir-AEs) were observed in 43% of patients receiving ipilimumab at 10 mg/kg and in 22% of patients receiving 3 mg/kg; the frequency of ir-AEs was not significantly different compared with previous studies of ipilimumab alone. Radiotherapy-related AEs were significantly more common in patients receiving higher doses of radiation. Palliation of symptoms was reported by 77% of patients after radiotherapy. Median OS was 9 and 39 months in patients receiving radiotherapy during induction and maintenance with ipilimumab, respectively. In this retrospective study, concurrent ipilimumab and radiotherapy was neither associated with higher than expected rates of AEs nor did it abrogate palliative effects of radiotherapy or survival benefits of ipilimumab. Further studies to prospectively explore the efficacy of this therapeutic combination are warranted.
MeSH term(s)	Adult ; Aged ; Antibodies, Monoclonal/therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Ipilimumab ; Male ; Melanoma/drug therapy ; Melanoma/radiotherapy ; Middle Aged ; Retrospective Studies ; Young Adult
Chemical Substances	Antibodies, Monoclonal ; Ipilimumab
Language	English
Publishing date	2013-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-13-0082
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Article: Dissecting the treatment-naive ecosystem of human melanoma brain metastasis

Biermann, Jana / Melms, Johannes C. / Amin, Amit Dipak / Wang, Yiping / Caprio, Lindsay A. / Karz, Alcida / Tagore, Somnath / Barrera, Irving / Ibarra-Arellano, Miguel A. / Andreatta, Massimo / Fullerton, Benjamin T. / Gretarsson, Kristjan H. / Sahu, Varun / Mangipudy, Vaibhav S. / Nguyen, Trang T.T. / Nair, Ajay / Rogava, Meri / Ho, Patricia / Koch, Peter D. /

Banu, Matei / Humala, Nelson / Mahajan, Aayushi / Walsh, Zachary H. / Shah, Shivem B. / Vaccaro, Daniel H. / Caldwell, Blake / Mu, Michael / Wünnemann, Florian / Chazotte, Margot / Berhe, Simon / Luoma, Adrienne M. / Driver, Joseph / Ingham, Matthew / Khan, Shaheer A. / Rapisuwon, Suthee / Slingluff, Craig L. / Eigentler, Thomas / Röcken, Martin / Carvajal, Richard / Atkins, Michael B. / Davies, Michael A. / Agustinus, Albert / Bakhoum, Samuel F. / Azizi, Elham / Siegelin, Markus / Lu, Chao / Carmona, Santiago J. / Hibshoosh, Hanina / Ribas, Antoni / Canoll, Peter / Bruce, Jeffrey N. / Bi, Wenya Linda / Agrawal, Praveen / Schapiro, Denis / Hernando, Eva / Macosko, Evan Z. / Chen, Fei / Schwartz, Gary K. / Izar, Benjamin

Cell. 2022 July 07, v. 185, no. 14

2022

Abstract: Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial ... ...

Abstract	Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBMs were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways. Key observations were validated in independent patient cohorts, patient-derived MBM/ECM xenograft models, RNA/ATAC-seq, proteomics, and multiplexed imaging. Integrated spatial analyses revealed distinct geography of putative cancer immune evasion and evidence for more abundant intra-tumoral B to plasma cell differentiation in lymphoid aggregates in MBM. MBM harbored larger fractions of monocyte-derived macrophages and dysfunctional TOX⁺CD8⁺ T cells with distinct expression of immune checkpoints. This work provides comprehensive insights into MBM biology and serves as a foundational resource for further discovery and therapeutic exploration.
Keywords	T-lymphocytes ; brain ; cell differentiation ; ecosystems ; geography ; humans ; immune evasion ; macrophages ; melanoma ; metastasis ; patients ; proteomics ; sequence analysis ; transcriptomics ; xenotransplantation
Language	English
Dates of publication	2022-0707
Size	p. 2591-2608.e30.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2022.06.007
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Dissecting the treatment-naive ecosystem of human melanoma brain metastasis.

Biermann, Jana / Melms, Johannes C / Amin, Amit Dipak / Wang, Yiping / Caprio, Lindsay A / Karz, Alcida / Tagore, Somnath / Barrera, Irving / Ibarra-Arellano, Miguel A / Andreatta, Massimo / Fullerton, Benjamin T / Gretarsson, Kristjan H / Sahu, Varun / Mangipudy, Vaibhav S / Nguyen, Trang T T / Nair, Ajay / Rogava, Meri / Ho, Patricia / Koch, Peter D /

Banu, Matei / Humala, Nelson / Mahajan, Aayushi / Walsh, Zachary H / Shah, Shivem B / Vaccaro, Daniel H / Caldwell, Blake / Mu, Michael / Wünnemann, Florian / Chazotte, Margot / Berhe, Simon / Luoma, Adrienne M / Driver, Joseph / Ingham, Matthew / Khan, Shaheer A / Rapisuwon, Suthee / Slingluff, Craig L / Eigentler, Thomas / Röcken, Martin / Carvajal, Richard / Atkins, Michael B / Davies, Michael A / Agustinus, Albert / Bakhoum, Samuel F / Azizi, Elham / Siegelin, Markus / Lu, Chao / Carmona, Santiago J / Hibshoosh, Hanina / Ribas, Antoni / Canoll, Peter / Bruce, Jeffrey N / Bi, Wenya Linda / Agrawal, Praveen / Schapiro, Denis / Hernando, Eva / Macosko, Evan Z / Chen, Fei / Schwartz, Gary K / Izar, Benjamin

Cell

2022 Volume 185, Issue 14, Page(s) 2591–2608.e30

Abstract	Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBM were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways. Key observations were validated in independent patient cohorts, patient-derived MBM/ECM xenograft models, RNA/ATAC-seq, proteomics, and multiplexed imaging. Integrated spatial analyses revealed distinct geography of putative cancer immune evasion and evidence for more abundant intra-tumoral B to plasma cell differentiation in lymphoid aggregates in MBM. MBM harbored larger fractions of monocyte-derived macrophages and dysfunctional TOX
MeSH term(s)	Brain Neoplasms/drug therapy ; Brain Neoplasms/secondary ; CD8-Positive T-Lymphocytes/pathology ; Ecosystem ; Humans ; Melanoma ; RNA-Seq
Language	English
Publishing date	2022-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2022.06.007
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19.

Bakouny, Ziad / Labaki, Chris / Grover, Punita / Awosika, Joy / Gulati, Shuchi / Hsu, Chih-Yuan / Alimohamed, Saif I / Bashir, Babar / Berg, Stephanie / Bilen, Mehmet A / Bowles, Daniel / Castellano, Cecilia / Desai, Aakash / Elkrief, Arielle / Eton, Omar E / Fecher, Leslie A / Flora, Daniel / Galsky, Matthew D / Gatti-Mays, Margaret E /

Gesenhues, Alicia / Glover, Michael J / Gopalakrishnan, Dharmesh / Gupta, Shilpa / Halfdanarson, Thorvardur R / Hayes-Lattin, Brandon / Hendawi, Mohamed / Hsu, Emily / Hwang, Clara / Jandarov, Roman / Jani, Chinmay / Johnson, Douglas B / Joshi, Monika / Khan, Hina / Khan, Shaheer A / Knox, Natalie / Koshkin, Vadim S / Kulkarni, Amit A / Kwon, Daniel H / Matar, Sara / McKay, Rana R / Mishra, Sanjay / Moria, Feras A / Nizam, Amanda / Nock, Nora L / Nonato, Taylor K / Panasci, Justin / Pomerantz, Lauren / Portuguese, Andrew J / Provenzano, Destie / Puc, Matthew / Rao, Yuan J / Rhodes, Terence D / Riely, Gregory J / Ripp, Jacob J / Rivera, Andrea V / Ruiz-Garcia, Erika / Schmidt, Andrew L / Schoenfeld, Adam J / Schwartz, Gary K / Shah, Sumit A / Shaya, Justin / Subbiah, Suki / Tachiki, Lisa M / Tucker, Matthew D / Valdez-Reyes, Melissa / Weissmann, Lisa B / Wotman, Michael T / Wulff-Burchfield, Elizabeth M / Xie, Zhuoer / Yang, Yuanchu James / Thompson, Michael A / Shah, Dimpy P / Warner, Jeremy L / Shyr, Yu / Choueiri, Toni K / Wise-Draper, Trisha M

JAMA oncology

2022 Volume 9, Issue 1, Page(s) 128–134

Abstract: Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.: Objective: To determine the association of baseline ... ...

Abstract	Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, setting, and participants: This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main outcomes and measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial registration: ClinicalTrials.gov Identifier: NCT04354701.
MeSH term(s)	Humans ; Female ; Middle Aged ; Aged ; Male ; COVID-19/epidemiology ; SARS-CoV-2 ; Cohort Studies ; Retrospective Studies ; COVID-19 Testing ; Cytokine Release Syndrome/etiology ; Immunosuppression Therapy ; Immunotherapy/adverse effects ; Neoplasms/epidemiology ; Neoplasms/therapy
Language	English
Publishing date	2022-11-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2374-2445
ISSN (online)	2374-2445
DOI	10.1001/jamaoncol.2022.5357
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Multimodal single-cell and whole-genome sequencing of small, frozen clinical specimens.

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Article: Characterizing metastatic uveal melanoma patients who develop symptomatic brain metastases.

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Article ; Online: Concurrent radiotherapy and ipilimumab immunotherapy for patients with melanoma.

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Article: Dissecting the treatment-naive ecosystem of human melanoma brain metastasis

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Article ; Online: Dissecting the treatment-naive ecosystem of human melanoma brain metastasis.

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Article ; Online: Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19.

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