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Article ; Online: Multiparametric in vitro and in vivo analysis of the safety profile of self-assembling peptides.

Ramirez-Labrada, Ariel / Santiago, Llipsy / Pesini, Cecilia / Arrieta, Marta / Arias, Maykel / Calvo Pérez, Adanays / Ciulla, Maria Gessica / Forouharshad, Mahdi / Pardo, Julian / Gálvez, Eva M / Gelain, Fabrizio

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4395

Abstract: Self-assembling peptides (SAPs) have gained significant attention in biomedicine because of their unique properties and ability to undergo molecular self-assembly driven by non-covalent interactions. By manipulating their composition and structure, SAPs ... ...

Abstract	Self-assembling peptides (SAPs) have gained significant attention in biomedicine because of their unique properties and ability to undergo molecular self-assembly driven by non-covalent interactions. By manipulating their composition and structure, SAPs can form well-ordered nanostructures with enhanced selectivity, stability and biocompatibility. SAPs offer advantages such as high chemical and biological diversity and the potential for functionalization. However, studies concerning its potentially toxic effects are very scarce, a limitation that compromises its potential translation to humans. This study investigates the potentially toxic effects of six different SAP formulations composed of natural amino acids designed for nervous tissue engineering and amenable to ready cross-linking boosting their biomechanical properties. All methods were performed in accordance with the relevant guidelines and regulations. A wound-healing assay was performed to evaluate how SAPs modify cell migration. The results in vitro demonstrated that SAPs did not induce genotoxicity neither skin sensitization. In vivo, SAPs were well-tolerated without any signs of acute systemic toxicity. Interestingly, SAPs were found to promote the migration of endothelial, macrophage, fibroblast, and neuronal-like cells in vitro, supporting a high potential for tissue regeneration. These findings contribute to the development and translation of SAP-based biomaterials for biomedical applications.
MeSH term(s)	Humans ; Peptides/chemistry ; Tissue Engineering/methods ; Neurons ; Biocompatible Materials/pharmacology ; Biocompatible Materials/chemistry ; Nanostructures/chemistry
Chemical Substances	Peptides ; Biocompatible Materials
Language	English
Publishing date	2024-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-54051-7
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Article ; Online: Granzyme-A deficiency attenuates experimental osteoarthritis in mice, but perforin deficiency does not.

Calvo, Jorge / Santiago, Llipsy / Arias, Maykel / Pardo, Julián / Albareda, Jorge / Martínez-Lostao, Luis / García-Alvarez, Felícito

Joint diseases and related surgery

2023 Volume 34, Issue 2, Page(s) 271–278

Abstract: Objectives: This study aims to assess the development of osteoarthritis (OA) in granzyme A- (gzmA) and B- (gzmB) and perforin- (perf) knockout mice.: Materials and methods: A total of 75 male and female C57BL/6 (eight to nine-week-old) mice were ... ...

Abstract	Objectives: This study aims to assess the development of osteoarthritis (OA) in granzyme A- (gzmA) and B- (gzmB) and perforin- (perf) knockout mice. Materials and methods: A total of 75 male and female C57BL/6 (eight to nine-week-old) mice were allocated to: gzmA-deficient (gzmA-/-) (11 females, 8 males), gzmB-deficient (gzmB-/-) (9 females, 8 males), perf-deficient (perf-/-) (10 females, 9 males), and control group (10 females, 10 males). Osteoarthritis was induced in the right knee by instability of the meniscus medial ligament. Sham surgery was practiced in the left knee. Knee samples obtained eight weeks after surgery were stained (Safranin-O) and blindly scored in lateral and medial femur and tibia using the Osteoarthritis Research Society International scale (OARSI) (from Grade 0, cartilage intact to 6, deformation), (five stages from 0, no OA to 4, >50% surface involvement); OARSI score (Grade x Stage); and a semi-quantitative scale from Grade 0 (normal) to 6 (cartilage erosion >80%). Results: Significantly higher values in all scales in the right knees compared to the left knees in male and female mice were observed (p<0.05). Males of all strains showed in the right knee higher values than females on all scales. Deficiency of perforin did not modify OA severity in any sex. The gzmA-/- females presented less degenerative changes than the other groups. Conclusion: Our study results show that sex plays an important role in the development of experimental OA in mice. Deficiency of gzmA can protect from the development of OA in female mice.
MeSH term(s)	Animals ; Female ; Male ; Mice ; Cartilage ; Granzymes/genetics ; Mice, Inbred C57BL ; Osteoarthritis/genetics ; Perforin/genetics
Chemical Substances	Granzymes (EC 3.4.21.-) ; Perforin (126465-35-8) ; Gzmb protein, mouse (EC 3.4.21.-)
Language	English
Publishing date	2023-04-27
Publishing country	Turkey
Document type	Journal Article
ISSN	2687-4792
ISSN (online)	2687-4792
DOI	10.52312/jdrs.2023.892
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Article ; Online: Hemizygous Granzyme A Mice Expressing the hSOD1G93A Transgene Show Slightly Extended Lifespan

Laura Moreno-Martinez / Llipsy Santiago / Miriam de la Torre / Ana Cristina Calvo / Julián Pardo / Rosario Osta

International Journal of Molecular Sciences, Vol 23, Iss 13554, p

2022 Volume 13554

Abstract: Granzyme A (gzmA), a serine protease involved in the modulation of the inflammatory immune response, is found at an elevated level in the serum from ALS patients. However, the influence of gzmA on the progression of ALS remains unclear. The aim of our ... ...

Abstract	Granzyme A (gzmA), a serine protease involved in the modulation of the inflammatory immune response, is found at an elevated level in the serum from ALS patients. However, the influence of gzmA on the progression of ALS remains unclear. The aim of our work was to assess whether the absence of gzmA in an ALS murine model could help slow down the progression of the disease. Homozygous and hemizygous gzmA-deficient mice expressing the hSOD1G93A transgene were generated, and survival of these mice was monitored. Subsequently, gene and protein expression of inflammatory and oxidative stress markers was measured in the spinal cord and quadriceps of these mice. We observed the longest lifespan in gzmA+/− mice. GzmA gene and protein expression was downregulated in the spinal cord and serum from gmzA+/− mice, confirming that the increased survival of hemizygous mice is correlated with lower levels of gzmA. In addition, mRNA and protein levels of glutathione reductase (GSR), involved in oxidative stress, were found downregulated in the spinal cord and quadriceps of gmzA+/− mice, together with lower IL-1β and IL-6 mRNA levels in hemyzigous mice. In summary, our findings indicate for the first time that reduced levels, but not the absence, of gzmA could slightly ameliorate the disease progression in this animal model.
Keywords	granzyme A ; SOD1G93A mouse ; inflammation ; glutathione reductase ; amyotrophic lateral sclerosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Hemizygous Granzyme A Mice Expressing the hSOD1G93A Transgene Show Slightly Extended Lifespan.

Moreno-Martinez, Laura / Santiago, Llipsy / de la Torre, Miriam / Calvo, Ana Cristina / Pardo, Julián / Osta, Rosario

International journal of molecular sciences

2022 Volume 23, Issue 21

Abstract	Granzyme A (gzmA), a serine protease involved in the modulation of the inflammatory immune response, is found at an elevated level in the serum from ALS patients. However, the influence of gzmA on the progression of ALS remains unclear. The aim of our work was to assess whether the absence of gzmA in an ALS murine model could help slow down the progression of the disease. Homozygous and hemizygous gzmA-deficient mice expressing the hSOD1G93A transgene were generated, and survival of these mice was monitored. Subsequently, gene and protein expression of inflammatory and oxidative stress markers was measured in the spinal cord and quadriceps of these mice. We observed the longest lifespan in gzmA+/- mice. GzmA gene and protein expression was downregulated in the spinal cord and serum from gmzA+/- mice, confirming that the increased survival of hemizygous mice is correlated with lower levels of gzmA. In addition, mRNA and protein levels of glutathione reductase (GSR), involved in oxidative stress, were found downregulated in the spinal cord and quadriceps of gmzA+/- mice, together with lower IL-1β and IL-6 mRNA levels in hemyzigous mice. In summary, our findings indicate for the first time that reduced levels, but not the absence, of gzmA could slightly ameliorate the disease progression in this animal model.
MeSH term(s)	Mice ; Animals ; Granzymes/metabolism ; Amyotrophic Lateral Sclerosis/genetics ; Longevity/genetics ; Spinal Cord/metabolism ; Disease Models, Animal ; Transgenes ; RNA, Messenger ; Mice, Transgenic ; Mice, Inbred C57BL ; Superoxide Dismutase/genetics
Chemical Substances	Granzymes (EC 3.4.21.-) ; RNA, Messenger ; Superoxide Dismutase (EC 1.15.1.1)
Language	English
Publishing date	2022-11-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232113554
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Article ; Online: The dynamics of neutralizing antibodies against SARS-CoV-2 in cats naturally exposed to virus reveals an increase in antibody activity after re-infection.

Villanueva-Saz, Sergio / Martínez, Marivi / Rueda, Pablo / Bolea, Sara / Pérez, María Dolores / Verde, Maite / Yzuel, Andrés / Hurtado-Guerrero, Ramón / Pardo, Julián / Santiago, Llipsy / Fernández, Antonio / Arias, Maykel

Veterinary research communications

2023 Volume 47, Issue 4, Page(s) 2179–2184

Abstract: Severe Acute Respiratory Syndrome Coronavirus 2 is the causative agent of Coronavirus Disease 2019 in humans. To date, little is known about the persistence of antibodies against SARS-CoV-2 in animals under natural conditions, in particular susceptible ... ...

Abstract	Severe Acute Respiratory Syndrome Coronavirus 2 is the causative agent of Coronavirus Disease 2019 in humans. To date, little is known about the persistence of antibodies against SARS-CoV-2 in animals under natural conditions, in particular susceptible pets such as cat. This study reports the detection and monitoring of the humoral response against SARS-CoV-2 including the detection of immunoglobulins G specific for receptor binding domain of SARS-CoV-2 spike protein by an enzyme-linked immunosorbent assay and neutralizing antibodies by virus neutralization assay. Results showed that these antibodies last longer than 16 months in two naturally apparently healthy infected cats with the absence of clinicopathological findings during the follow-up. Moreover, re-infection is also possible with an important increase in virus neutralization test titers in both animals with no evident systemic signs found during each physical examination and with values of hematologic and biochemical parameters inside the normal reference intervals. Our results confirm a slow but progressive decrease of the kinetics and immunity of neutralizing antibodies in cats after the infection. Furthermore, similar to humans SARS-CoV-2 reinfection can stimulate an increase of the neutralizing antibodies determined by these two serological techniques in domestic cats.
MeSH term(s)	Cats ; Animals ; Humans ; SARS-CoV-2 ; Antibodies, Neutralizing ; Reinfection/veterinary ; COVID-19/veterinary ; Antibodies, Viral ; Cat Diseases
Chemical Substances	spike protein, SARS-CoV-2 ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2023-03-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	406735-6
ISSN	1573-7446 ; 0165-7380
ISSN (online)	1573-7446
ISSN	0165-7380
DOI	10.1007/s11259-023-10087-0
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Article ; Online: Mouse Model of Colitis-Associated Colorectal Cancer (CAC): Isolation and Characterization of Mucosal-Associated Lymphoid Cells.

Santiago, Llipsy / Castro, Marta / Pardo, Julián / Arias, Maykel

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

2018 Volume 1884, Page(s) 189–202

Abstract: Colorectal cancer (CRC) is the third most common malignancy worldwide presenting high mortality due to low treatment efficacy. Existing evidence indicates that inflammatory bowel disease (IBD) is associated with a higher risk of developing CRC. Many ... ...

Abstract	Colorectal cancer (CRC) is the third most common malignancy worldwide presenting high mortality due to low treatment efficacy. Existing evidence indicates that inflammatory bowel disease (IBD) is associated with a higher risk of developing CRC. Many murine models of inflammation-related colon carcinogenesis (CAC) have been developed to study colon carcinogenesis and novel treatments. A commonly used model involves the combination of a single dose of azoxymethane (AOM), together with three cycles of the inflammatory agent dextran sodium sulfate (DSS) (5 days in drinking water followed by a two-week rest). Following this protocol, around 50% of the animals develop CRCs after 45 days and almost 100% of animals after 60 days. During CAC development, immune cells, cytokines, and other immune mediators are involved in both tumorigenesis and the elimination of cancer cells during immunotherapy. Thus, the study of mucosal immune responses (including lamina propria mononuclear cells and intraepithelial lymphocytes) is important to understand the role of the immune system during development and therapy in CRC. Single immune cell suspensions from lamina propria and epithelium can be purified combining selective tissue digestion and Percoll gradient centrifugation. Isolated cells can be characterized using flow cytometry by analyzing surface antigens or intracellular cytokines and cytotoxic mediators or employed for further investigations like comparative studies of mRNA expression, cell-proliferation assay, protein analysis, or even functional cytotoxicity assays. The CAC model is useful to study the involvement of immune cells not only during the carcinogenesis process but, in addition, during the treatment with novel immunotherapy protocols.
MeSH term(s)	Animals ; Azoxymethane/administration & dosage ; Azoxymethane/toxicity ; Cell Separation/instrumentation ; Cell Separation/methods ; Cell Transformation, Neoplastic/chemically induced ; Cell Transformation, Neoplastic/immunology ; Cell Transformation, Neoplastic/pathology ; Centrifugation, Density Gradient/instrumentation ; Centrifugation, Density Gradient/methods ; Colitis, Ulcerative/chemically induced ; Colitis, Ulcerative/immunology ; Colitis, Ulcerative/pathology ; Colon/cytology ; Colon/immunology ; Colon/pathology ; Colorectal Neoplasms/etiology ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/pathology ; Dextran Sulfate/administration & dosage ; Dextran Sulfate/toxicity ; Flow Cytometry/instrumentation ; Flow Cytometry/methods ; Humans ; Intestinal Mucosa/cytology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/pathology ; Lymphocytes/drug effects ; Lymphocytes/immunology ; Lymphocytes/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasms, Experimental/chemically induced ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/pathology
Chemical Substances	Dextran Sulfate (9042-14-2) ; Azoxymethane (MO0N1J0SEN)
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_13
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Article: Inflammatory cell death induced by cytotoxic lymphocytes: a dangerous but necessary liaison

de Miguel, Diego / Ramirez‐Labrada, Ariel / Uranga, Iratxe / Hidalgo, Sandra / Santiago, Llipsy / Galvez, Eva María / Arias, Maykel / Pardo, Julián

FEBS journal. 2022 Aug., v. 289, no. 15

2022

Abstract: Cytotoxic lymphocytes (CLs), and more specifically Tc and NK cells, are the main executors of cell death in the immune system, playing a key role during both immunosurveillance and immunotherapy. These cells induce regulated cell death (RCD) by different ...

Abstract	Cytotoxic lymphocytes (CLs), and more specifically Tc and NK cells, are the main executors of cell death in the immune system, playing a key role during both immunosurveillance and immunotherapy. These cells induce regulated cell death (RCD) by different mechanisms, being granular exocytosis and expression of death ligands the most prominent and best characterized ones. Apoptosis, a traditionally considered low‐inflammatory type of cell death, has been accepted for years as the paradigm of RCD induced by CLs. However, several recent studies have demonstrated that NK cells and Tc cells can also induce more inflammatory forms of cell death, namely, necroptosis, pyroptosis, and ferroptosis. Activation of these highly inflammatory types of cell death appears to critically contribute to the activation of a successful antitumour immune response. Additionally, the role of specific cell death pathways in immunogenic cell death is still under intense debate, especially considering the interconnections with other inflammatory forms of cell death. These evidences, together with the advent of new cancer immunotherapies, highlight the necessity to deepen our understanding of the link between the cell death triggered by CLs and inflammation. This knowledge will be instrumental to maximize the antitumour potential of immunotherapies, minimizing deleterious effects associated with these treatments. In this review, we will briefly summarize the main features of apoptosis, necroptosis, pyroptosis and ferroptosis, to subsequently discuss the most recent evidences about the role of these RCD pathways during the elimination of cancer cells mediated by CLs and its modulation to increase the efficacy of cancer immunotherapy.
Keywords	antineoplastic activity ; cytotoxicity ; exocytosis ; ferroptosis ; immune response ; immunotherapy ; inflammation ; ligands ; necroptosis ; pyroptosis
Language	English
Dates of publication	2022-08
Size	p. 4398-4415.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16093
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Inflammatory cell death induced by cytotoxic lymphocytes: a dangerous but necessary liaison.

de Miguel, Diego / Ramirez-Labrada, Ariel / Uranga, Iratxe / Hidalgo, Sandra / Santiago, Llipsy / Galvez, Eva María / Arias, Maykel / Pardo, Julián

The FEBS journal

2021 Volume 289, Issue 15, Page(s) 4398–4415

Abstract	Cytotoxic lymphocytes (CLs), and more specifically Tc and NK cells, are the main executors of cell death in the immune system, playing a key role during both immunosurveillance and immunotherapy. These cells induce regulated cell death (RCD) by different mechanisms, being granular exocytosis and expression of death ligands the most prominent and best characterized ones. Apoptosis, a traditionally considered low-inflammatory type of cell death, has been accepted for years as the paradigm of RCD induced by CLs. However, several recent studies have demonstrated that NK cells and Tc cells can also induce more inflammatory forms of cell death, namely, necroptosis, pyroptosis, and ferroptosis. Activation of these highly inflammatory types of cell death appears to critically contribute to the activation of a successful antitumour immune response. Additionally, the role of specific cell death pathways in immunogenic cell death is still under intense debate, especially considering the interconnections with other inflammatory forms of cell death. These evidences, together with the advent of new cancer immunotherapies, highlight the necessity to deepen our understanding of the link between the cell death triggered by CLs and inflammation. This knowledge will be instrumental to maximize the antitumour potential of immunotherapies, minimizing deleterious effects associated with these treatments. In this review, we will briefly summarize the main features of apoptosis, necroptosis, pyroptosis and ferroptosis, to subsequently discuss the most recent evidences about the role of these RCD pathways during the elimination of cancer cells mediated by CLs and its modulation to increase the efficacy of cancer immunotherapy.
MeSH term(s)	Antineoplastic Agents ; Apoptosis ; Cell Death ; Killer Cells, Natural ; Necroptosis ; Pyroptosis
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2021-07-17
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16093
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Article ; Online: Seroprevalence of anti-SARS-CoV-2 antibodies in household domestic ferrets (Mustela putorius furo) in Spain, 2019-2023.

Giner, Jacobo / Lebrero, María Eugenia / Trotta, Michele / Rueda, Pablo / Vilalta, Laura / Verde, Maite / Hurtado-Guerrero, Ramón / Pardo, Julián / Lacasta, Delia / Santiago, Llipsy / Arias, Maykel / Peña-Fresneda, Natacha / Montesinos, Andrés / Pérez, María D / Fernández, Antonio / Villanueva-Saz, Sergio

Veterinary research communications

2023 Volume 48, Issue 1, Page(s) 533–540

Abstract: SARS-CoV-2 is the causal agent of Coronavirus Disease 2019 (COVID-19) in humans that emerged in late 2019. This virus is able to infect humans and different animal species. Among pets, cats and ferrets are more susceptible to be infected by the SARS-CoV- ... ...

Abstract	SARS-CoV-2 is the causal agent of Coronavirus Disease 2019 (COVID-19) in humans that emerged in late 2019. This virus is able to infect humans and different animal species. Among pets, cats and ferrets are more susceptible to be infected by the SARS-CoV-2. Epidemiological studies are an important tool to provide information under natural conditions of exposure to SARS-CoV-2 virus. In comparison to cats, limited epidemiological studies have been performed in domestic ferrets (Mustela putorius furo) reporting the presence of antibodies in this species. This study analysed the presence of anti-SARS-CoV-2 antibodies in 432 cliend-owned ferrets from different geographical areas of Spain during the different waves of COVID-19 outbreaks from December 2019 to May 2023 (42 months). For this purpose, anti-SARS-CoV-2 antibodies were detected by an enzyme-linked immunosorbent method (ELISA) using the receptor binding domain (RBD) of Spike antigen and confirmed by serum virus neutralization assay. Eighteen of the 432 ferrets included were seroreactive by the in-house ELISA (4.17%, 95% Confidence Interval (CI): 2.65-6.49). In this sense, the wave of COVID-19 with the higher number of seropositive ferrets occurred during the seventh wave when the different Omicron subvariants were the dominant virus variants. Our results suggest that the risk of SARS-CoV-2 transmission in domestic ferrets in natural conditions is low. Further research is need to evaluate the potential risk of transmission of SARS-CoV-2 from human to pets.
MeSH term(s)	Animals ; Humans ; Ferrets ; COVID-19/epidemiology ; COVID-19/veterinary ; SARS-CoV-2 ; Seroepidemiologic Studies ; Spain/epidemiology ; Antibodies, Viral
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2023-08-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	406735-6
ISSN	1573-7446 ; 0165-7380
ISSN (online)	1573-7446
ISSN	0165-7380
DOI	10.1007/s11259-023-10190-2
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Article ; Online: PD-1 is expressed in cytotoxic granules of NK cells and rapidly mobilized to the cell membrane following recognition of tumor cells.

Pesini, Cecilia / Hidalgo, Sandra / Arias, Maykel A / Santiago, Llipsy / Calvo, Carlota / Ocariz-Díez, Maitane / Isla, Dolores / Lanuza, Pilar M / Agustín, M José / Galvez, Eva M / Ramírez-Labrada, Ariel / Pardo, Julián

Oncoimmunology

2022 Volume 11, Issue 1, Page(s) 2096359

Abstract: The contribution of the T cell-related inhibitory checkpoint PD-1 to the regulation of NK cell activity is still not clear with contradictory results concerning its expression and role in the modulation of NK cell cytotoxicity. We provide novel key ... ...

Abstract	The contribution of the T cell-related inhibitory checkpoint PD-1 to the regulation of NK cell activity is still not clear with contradictory results concerning its expression and role in the modulation of NK cell cytotoxicity. We provide novel key findings on the mechanism involved in the regulation of PD-1 expression on NK cell membrane and its functional consequences for the elimination of cancer cells. In contrast to freshly isolated NK cells from cancer patients, those from healthy donors did not express PD-1 on the cell membrane. However, when healthy NK cells were incubated with tumor target cells, membrane PD-1 expression increased, concurrent with the CD107a surface mobilization. This finding suggested that PD-1 was translocated to the cell membrane during NK cell degranulation after contact with target cells. Indeed, cytosolic PD-1 was expressed in freshly-isolated-NK cells and partly co-localized with CD107a and GzmB, confirming that membrane PD-1 corresponded to a pool of preformed PD-1. Moreover, NK cells that had mobilized PD-1 to the cell membrane presented a significantly reduced anti-tumor activity on PD-L1-expressing-tumor cells
MeSH term(s)	Antineoplastic Agents ; Cell Membrane/metabolism ; Humans ; Immunotherapy ; Killer Cells, Natural/metabolism ; Lymphocyte Activation ; Neoplasms
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2022-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.1080/2162402X.2022.2096359
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