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Article ; Online: Intratumor Heterogeneity and Antitumor Immunity Shape One Another Bidirectionally.

Wolf, Yochai / Samuels, Yardena

Clinical cancer research : an official journal of the American Association for Cancer Research

2022 Volume 28, Issue 14, Page(s) 2994–3001

Abstract: Over the last decade, it has become clear that the genomic landscapes of tumors profoundly impact their immunogenicity and how tumor cells interact with immune cells. Whereas past discoveries mainly focused on the interplay between tumor immunogenicity ... ...

Abstract	Over the last decade, it has become clear that the genomic landscapes of tumors profoundly impact their immunogenicity and how tumor cells interact with immune cells. Whereas past discoveries mainly focused on the interplay between tumor immunogenicity and tumor mutational burden (TMB), under the assumption that a higher mutation load would give rise to a better patient response to immune checkpoint blockade therapies, we and others have underlined intratumor heterogeneity (ITH) as an important determinant of the magnitude of the antitumor response and the nature of the tumor microenvironment. In this review, we define TMB versus ITH and how the two factors are being inferred from data, examine key findings in the cancer immunogenomics literature deciphering the complex cross-talk between TMB, ITH, and antitumor immunity in human cancers and in vivo models, and discuss the mutual influence of ITH and immunity-how the antitumor response can give rise to tumors with higher ITH, and how higher ITH can put shackles on the antitumor response.
MeSH term(s)	Antigens, Neoplasm ; Biomarkers, Tumor/genetics ; Genetic Heterogeneity ; Humans ; Mutation ; Neoplasms/genetics ; Tumor Microenvironment/genetics
Chemical Substances	Antigens, Neoplasm ; Biomarkers, Tumor
Language	English
Publishing date	2022-04-05
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-21-1355
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 4223: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
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Article ; Online: The landscape of T cell antigens for cancer immunotherapy.

Peri, Aviyah / Salomon, Nadja / Wolf, Yochai / Kreiter, Sebastian / Diken, Mustafa / Samuels, Yardena

Nature cancer

2023 Volume 4, Issue 7, Page(s) 937–954

Abstract: The remarkable capacity of immunotherapies to induce durable regression in some patients with metastatic cancer relies heavily on T cell recognition of tumor-presented antigens. As checkpoint-blockade therapy has limited efficacy, tumor antigens have the ...

Abstract	The remarkable capacity of immunotherapies to induce durable regression in some patients with metastatic cancer relies heavily on T cell recognition of tumor-presented antigens. As checkpoint-blockade therapy has limited efficacy, tumor antigens have the potential to be exploited for complementary treatments, many of which are already in clinical trials. The surge of interest in this topic has led to the expansion of the tumor antigen landscape with the emergence of new antigen categories. Nonetheless, how different antigens compare in their ability to elicit efficient and safe clinical responses remains largely unknown. Here, we review known cancer peptide antigens, their attributes and the relevant clinical data and discuss future directions.
MeSH term(s)	Humans ; Immunotherapy ; Neoplasms/therapy ; T-Lymphocytes ; Antigens, Neoplasm
Chemical Substances	Antigens, Neoplasm
Language	English
Publishing date	2023-07-06
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-023-00588-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Author Correction: Breaking the performance ceiling for neoantigen immunogenicity prediction.

O'Brien, Hugh / Salm, Max / Morton, Laura T / Szukszto, Maciej / O'Farrell, Felix / Boulton, Charlotte / Becker, Pablo D / Samuels, Yardena / Swanton, Charles / Mansour, Marc R / Reker Hadrup, Sine / Quezada, Sergio A

Nature cancer

2024

Language	English
Publishing date	2024-04-15
Publishing country	England
Document type	Published Erratum
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-024-00767-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mechanisms of immune activation and regulation: lessons from melanoma.

Kalaora, Shelly / Nagler, Adi / Wargo, Jennifer A / Samuels, Yardena

Nature reviews. Cancer

2022 Volume 22, Issue 4, Page(s) 195–207

Abstract: Melanoma, a skin cancer that develops from pigment cells, has been studied intensively, particularly in terms of the immune response to tumours, and has been used as a model for the development of immunotherapy. This is due, in part, to the high ... ...

Abstract	Melanoma, a skin cancer that develops from pigment cells, has been studied intensively, particularly in terms of the immune response to tumours, and has been used as a model for the development of immunotherapy. This is due, in part, to the high mutational burden observed in melanomas, which increases both their immunogenicity and the infiltration of immune cells into the tumours, compared with other types of cancers. The immune response to melanomas involves a complex set of components and interactions. As the tumour evolves, it accumulates an increasing number of genetic and epigenetic alterations, some of which contribute to the immunogenicity of the tumour cells and the infiltration of immune cells. However, tumour evolution also enables the development of resistance mechanisms, which, in turn, lead to tumour immune escape. Understanding the interactions between melanoma tumour cells and the immune system, and the evolving changes within the melanoma tumour cells, the immune system and the microenvironment, is essential for the development of new cancer therapies. However, current research suggests that other extrinsic factors, such as the microbiome, may play a role in the immune response to melanomas. Here, we review the mechanisms underlying the immune response in the tumour and discuss recent advances as well as strategies for treatment development.
MeSH term(s)	Humans ; Immunotherapy ; Melanoma/genetics ; Skin Neoplasms/pathology ; Tumor Escape/genetics ; Tumor Microenvironment
Language	English
Publishing date	2022-02-01
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/s41568-022-00442-9
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Zs.A 5563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 24: Show issues

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Article ; Online: PIK3CA in cancer: The past 30 years.

Arafeh, Rand / Samuels, Yardena

Seminars in cancer biology

2019 Volume 59, Page(s) 36–49

Abstract: Almost thirty years ago, PI3K was discovered as a lipid kinase associated with certain oncoproteins. The first decade of research on PI3K saw the identification, purification and cloning of PI3Kα. The second decade of research was noted for the ... ...

Abstract	Almost thirty years ago, PI3K was discovered as a lipid kinase associated with certain oncoproteins. The first decade of research on PI3K saw the identification, purification and cloning of PI3Kα. The second decade of research was noted for the identification of some of PI3K's activators and effectors. This was accompanied by the discovery that PI3K acts as a retroviral oncogene. The third decade was known for the establishment of the direct involvement of PI3K in cancer, demonstrated by the identification of cancer-specific mutations. Efforts to target PI3K were on the rise from that moment on, accompanied by the first clinical trials for PI3K inhibitor therapies. In the fourth decade of research, PI3K-based cancer drugs will continue to emerge, as will new knowledge regarding other uncovered functions of this protein and pathway.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors ; Class I Phosphatidylinositol 3-Kinases/genetics ; Class I Phosphatidylinositol 3-Kinases/metabolism ; Gain of Function Mutation ; Humans ; Molecular Targeted Therapy ; Mutation ; Neoplasms/drug therapy ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Phosphoinositide-3 Kinase Inhibitors/therapeutic use
Chemical Substances	Antineoplastic Agents ; Phosphoinositide-3 Kinase Inhibitors ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; PIK3CA protein, human (EC 2.7.1.137)
Language	English
Publishing date	2019-02-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2019.02.002
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Zs.A 2922: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: Cancer research in the era of immunogenomics.

Wolf, Yochai / Samuels, Yardena

ESMO open

2018 Volume 3, Issue 7, Page(s) e000475

Abstract: The most meaningful advancement in cancer treatment in recent years has been the emergence of immunotherapy. Checkpoint inhibitor blockade and adoptive T cell therapy have shown remarkable clinical effects in a wide range of tumour types. Despite these ... ...

Abstract	The most meaningful advancement in cancer treatment in recent years has been the emergence of immunotherapy. Checkpoint inhibitor blockade and adoptive T cell therapy have shown remarkable clinical effects in a wide range of tumour types. Despite these advances, many tumours do not respond to these treatments, which raises the need to further investigate how patients can benefit from immunotherapy. This effort can now take advantage of the recent technological progress in single-cell, high-throughput sequencing and computational efforts. In this review, we will discuss advances in different immunotherapies and the principles of cancer immunogenomics, with an emphasis on the detection of cancer neoantigens with human leucocyte antigen peptidomics, and how these principles can be further used for more efficient clinical output.
Language	English
Publishing date	2018-12-26
Publishing country	England
Document type	Journal Article ; Review
ISSN	2059-7029
ISSN	2059-7029
DOI	10.1136/esmoopen-2018-000475
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Article ; Online: NRas activity is regulated by dynamic interactions with nanoscale signaling clusters at the plasma membrane.

Yakovian, Oren / Sajman, Julia / Alon, Michal / Arafeh, Rand / Samuels, Yardena / Sherman, Eilon

iScience

2022 Volume 25, Issue 11, Page(s) 105282

Abstract: NRas is a key mediator of the mitogenic pathway in normal cells and in cancer cells. Its dynamics and nanoscale organization at the plasma membrane (PM) facilitate its signaling. Here, we used two-color photoactivated localization microscopy to resolve ... ...

Abstract	NRas is a key mediator of the mitogenic pathway in normal cells and in cancer cells. Its dynamics and nanoscale organization at the plasma membrane (PM) facilitate its signaling. Here, we used two-color photoactivated localization microscopy to resolve the organization of individual NRas and associated signaling proteins in live melanoma cells, with resolution down to ∼20 nm. Upon EGF activation, a fraction of NRas and BRAF (dis)assembled synchronously at the PM in co-clusters. NRas and BRAF clusters associated with GPI-enriched domains, serving as possible nucleation sites for these clusters. NRas and BRAF association in mutual clusters was reduced by the NRas farnesylation inhibitor lonafarnib, yet enhanced by the BRAF inhibitor vemurafenib. Surprisingly, dispersed NRas molecules associated with the periphery of self-clusters of either Grb2 or NF1. Thus, NRas-mediated signaling, which is critical in health and disease, is regulated by dynamic interactions with functional clusters of BRAF or other related proteins at the PM.
Language	English
Publishing date	2022-10-09
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.105282
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Analysis of Enzymatic Activity of Matrix Metalloproteinase (MMP) by Collagen Zymography in Melanoma.

Walia, Vijay / Samuels, Yardena

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1731, Page(s) 97–106

Abstract: Protein zymography is the most commonly used technique to study the enzymatic activity of matrix metalloproteinases (MMPs) and their inhibitors. MMPs are proteolytic enzymes that promote extracellular matrix degradation. MMPs are frequently mutated in ... ...

Abstract	Protein zymography is the most commonly used technique to study the enzymatic activity of matrix metalloproteinases (MMPs) and their inhibitors. MMPs are proteolytic enzymes that promote extracellular matrix degradation. MMPs are frequently mutated in malignant melanomas as well as other cancers and are linked to increasing incidence of tumor metastasis. Substrate zymography characterizes MMP activity by their ability to degrade preferred substrates. Here we describe the collagen zymography technique to measure the active or latent form of MMPs using MMP-8 as an example, which is a frequently mutated MMP family member in malignant melanomas. The same technique can be used with the modification of substrate to detect metalloproteinase activity of other MMPs. Both wild-type and mutated forms of MMPs can be analyzed using a single gel using this method.
MeSH term(s)	Collagen/metabolism ; Electrophoresis, Polyacrylamide Gel/instrumentation ; Electrophoresis, Polyacrylamide Gel/methods ; Enzyme Assays/instrumentation ; Enzyme Assays/methods ; HEK293 Cells ; Humans ; Matrix Metalloproteinase 8/analysis ; Matrix Metalloproteinase 8/genetics ; Matrix Metalloproteinase 8/metabolism ; Melanoma/genetics ; Proteolysis
Chemical Substances	Collagen (9007-34-5) ; MMP8 protein, human (EC 3.4.24.34) ; Matrix Metalloproteinase 8 (EC 3.4.24.34)
Language	English
Publishing date	2018-01-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7595-2_10
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cancer Exome-Based Identification of Tumor Neo-Antigens Using Mass Spectrometry.

Kalaora, Shelly / Samuels, Yardena

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1884, Page(s) 203–214

Abstract: Neo-antigens expressed on tumors are targets for development of cancer immunotherapy strategies. Use of prediction algorithms to identify neo-antigens yields a significant number of peptides that must be validated in laborious and time-consuming methods; ...

Abstract	Neo-antigens expressed on tumors are targets for development of cancer immunotherapy strategies. Use of prediction algorithms to identify neo-antigens yields a significant number of peptides that must be validated in laborious and time-consuming methods; many prove to be false-positive identifications. The use of HLA peptidomics allows the isolation of the HLA-peptide complexes directly from cells and can be done on fresh tumor, patient-derived xerographs, or cell lines when the tissue sample is limited. This method can be used to identify both HLA class I and HLA class II or any different MHC from different species. Here we describe the steps to create the immune-affinity columns used from the process, the immunoprecipitation procedure, and also the isolation of the peptides that will be analyzed by mass spectrometry.
MeSH term(s)	Algorithms ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/immunology ; Antigens, Neoplasm/isolation & purification ; Cell Culture Techniques/instrumentation ; Cell Culture Techniques/methods ; Chromatography, High Pressure Liquid/instrumentation ; Chromatography, High Pressure Liquid/methods ; Exome/genetics ; Exome/immunology ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class I/isolation & purification ; Histocompatibility Antigens Class II/genetics ; Histocompatibility Antigens Class II/immunology ; Histocompatibility Antigens Class II/isolation & purification ; Humans ; Hybridomas ; Immunoprecipitation/instrumentation ; Immunoprecipitation/methods ; Neoplasms/immunology ; Neoplasms/pathology ; Proteomics/instrumentation ; Proteomics/methods ; Spectrometry, Mass, Electrospray Ionization/instrumentation ; Spectrometry, Mass, Electrospray Ionization/methods ; Tandem Mass Spectrometry/instrumentation ; Tandem Mass Spectrometry/methods
Chemical Substances	Antigens, Neoplasm ; Histocompatibility Antigens Class I ; Histocompatibility Antigens Class II
Language	English
Publishing date	2018-11-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-8885-3_14
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Article ; Online: Breaking the performance ceiling for neoantigen immunogenicity prediction.

Nature cancer

2023 Volume 4, Issue 12, Page(s) 1618–1621

MeSH term(s)	Antigens, Neoplasm/genetics ; Humans
Chemical Substances	Antigens, Neoplasm
Language	English
Publishing date	2023-12-22
Publishing country	England
Document type	Journal Article
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-023-00675-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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