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Article ; Online: Human T lymphocytes at tumor sites.

Notarbartolo, Samuele / Abrignani, Sergio

2022 Volume 44, Issue 6, Page(s) 883–901

Abstract: ... ...

Abstract	CD4
MeSH term(s)	Humans ; Lymphocyte Count ; Lymphoid Tissue ; Immunologic Surveillance ; Immunotherapy ; Memory T Cells
Language	English
Publishing date	2022-11-16
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-022-00970-4
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Article ; Online: Human T lymphocytes at tumor sites

Notarbartolo, Samuele / Abrignani, Sergio

Semin Immunopathol. 2022 Nov., v. 44, no. 6, p. 883-901

2022 , Page(s) 883–901

Abstract: CD4⁺ and CD8⁺ T lymphocytes mediate most of the adaptive immune response against tumors. Naïve T lymphocytes specific for tumor antigens are primed in lymph nodes by dendritic cells. Upon activation, antigen-specific T cells proliferate and differentiate ...

Abstract	CD4⁺ and CD8⁺ T lymphocytes mediate most of the adaptive immune response against tumors. Naïve T lymphocytes specific for tumor antigens are primed in lymph nodes by dendritic cells. Upon activation, antigen-specific T cells proliferate and differentiate into effector cells that migrate out of peripheral blood into tumor sites in an attempt to eliminate cancer cells. After accomplishing their function, most effector T cells die in the tissue, while a small fraction of antigen-specific T cells persist as long-lived memory cells, circulating between peripheral blood and lymphoid tissues, to generate enhanced immune responses when re-encountering the same antigen. A subset of memory T cells, called resident memory T (TRM) cells, stably resides in non-lymphoid peripheral tissues and may provide rapid immunity independently of T cells recruited from blood. Being adapted to the tissue microenvironment, TRM cells are potentially endowed with the best features to protect against the reemergence of cancer cells. However, when tumors give clinical manifestation, it means that tumor cells have evaded immune surveillance, including that of TRM cells. Here, we review the current knowledge as to how TRM cells are generated during an immune response and then maintained in non-lymphoid tissues. We then focus on what is known about the role of CD4⁺ and CD8⁺ TRM cells in antitumor immunity and their possible contribution to the efficacy of immunotherapy. Finally, we highlight some open questions in the field and discuss how new technologies may help in addressing them.
Keywords	adaptive immunity ; antigens ; blood ; humans ; immune response ; immunotherapy ; lymph ; memory ; monitoring ; neoplasms
Language	English
Dates of publication	2022-11
Size	p. 883-901
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
Note	Review
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-022-00970-4
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Protocol for the detection of defined T cell clones in a heterogeneous cell population.

Gobbini, Andrea / Bandera, Alessandra / Grifantini, Renata / Abrignani, Sergio / Notarbartolo, Samuele

STAR protocols

2023 Volume 5, Issue 1, Page(s) 102787

Abstract: Identifying defined T cell clones within a polyclonal population is key to clarifying their phenotype and function. Here, we present a protocol for detecting specified T cell clones in a heterogeneous cell population. We describe steps for stimulating ... ...

Abstract	Identifying defined T cell clones within a polyclonal population is key to clarifying their phenotype and function. Here, we present a protocol for detecting specified T cell clones in a heterogeneous cell population. We describe steps for stimulating human CD4
MeSH term(s)	Humans ; T-Lymphocytes ; Receptors, Antigen, T-Cell/genetics ; Clone Cells ; Flow Cytometry
Chemical Substances	Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Journal Article
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2023.102787
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Article: Flow diversion for indirect carotid-cavernous fistula: Still an off-label indication?

Brunasso, Lara / Casamassima, Nicola / Abrignani, Sergio / Sturiale, Carmelo Lucio / Incandela, Francesca / Giammalva, Giuseppe Roberto / Iacopino, Domenico Gerardo / Maugeri, Rosario / Craparo, Giuseppe

Surgical neurology international

2023 Volume 14, Page(s) 65

Abstract: Background: Flow diversion (FD) is an established treatment for large or giant wide-necked unruptured intracranial aneurysms. In the past few years, the use of flow diverter devices was extended to several other "off-label" indications, including ... ...

Abstract	Background: Flow diversion (FD) is an established treatment for large or giant wide-necked unruptured intracranial aneurysms. In the past few years, the use of flow diverter devices was extended to several other "off-label" indications, including solitary or adjunctive treatment to coil embolization for direct (Barrow A type) carotid cavernous fistulas (CCFs). The use of liquid embolic agents still represents the first-line treatment for indirect CCFs. Typically, the ipsilateral inferior petrosal sinus or superior ophthalmic vein (SOV) is the preferred transvenous routes to access CCFs. In some cases, vessel tortuosity or different features make the endovascular access challenging, thus requiring different approaches and strategies. The aim of the study is to discuss rational and technical aspect in treating indirect CCFs referring to the most up-to-date literature. An alternative experience-based endovascular strategy with FD is described. Methods: We report the case of a 54-year-old woman diagnosed with indirect CCF and treated with flow diverter stent. Results: After multiple unsuccessful attempts at transarterial right SOV catheterization, a right indirect CCF fed by a single trunk at the ophthalmic origin from the internal carotid artery (ICA) was treated by ICA stand-alone FD. Blood flow was redirect and successfully reduced through the fistula, with immediately postprocedure improvement of the patient's clinical status (ipsilateral proptosis and chemosis). Ten-months radiological follow-up showed the complete obliteration of the fistula. No adjunctive endovascular treatment was performed. Conclusion: FD appears a reasonable alternative stand-alone endovascular strategy also for selected difficult-to-access indirect CCFs, when all conventional routes are judged unfeasible. Further investigations will be necessary to better define and support this potential lesson-learned application.
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Journal Article
ISSN	2229-5097
ISSN	2229-5097
DOI	10.25259/SNI_1113_2022
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Article ; Online: Identification of Lymphangioleiomyomatosis-associated Serum MicroRNAs.

Rossi, Riccardo L / Elia, Davide / Torre, Olga / Cassandro, Roberto / Caminati, Antonella / Bulgheroni, Elisabetta / Carelli, Elena / Vasco, Chiara / Abrignani, Sergio / Geginat, Jens / Harari, Sergio

American journal of respiratory cell and molecular biology

2024 Volume 70, Issue 2, Page(s) 146–148

MeSH term(s)	Humans ; Lymphangioleiomyomatosis/genetics ; MicroRNAs/genetics ; Lung ; Lung Neoplasms/genetics
Chemical Substances	MicroRNAs
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Letter
ZDB-ID	1025960-0
ISSN	1535-4989 ; 1044-1549
ISSN (online)	1535-4989
ISSN	1044-1549
DOI	10.1165/rcmb.2023-0243LE
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Article ; Online: Characterization of human CD4

Pulvirenti, Nadia / Silvetri, Ylenia / Clemente, Francesca / Bosotti, Roberto / Carelli, Elena / Moschetti, Giorgia / Gruarin, Paola / Vasco, Chiara / Crosti, Maria Cristina / Sarnicola, Maria Lucia / Valenti, Luca / Prati, Daniele / Abrignani, Sergio / Geginat, Jens

European journal of immunology

2024 Volume 54, Issue 4, Page(s) e2350675

Abstract: ... Human ... ...

Abstract	Human CD4
MeSH term(s)	Humans ; Interleukin-10 ; T-Lymphocyte Subsets ; T-Lymphocytes, Regulatory ; CD4-Positive T-Lymphocytes ; Th1 Cells ; Cell Differentiation ; T-Box Domain Proteins/genetics
Chemical Substances	Interleukin-10 (130068-27-8) ; EOMES protein, human ; T-Box Domain Proteins
Language	English
Publishing date	2024-02-23
Publishing country	Germany
Document type	Journal Article
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202350675
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Article ; Online: mTOR-dependent translation drives tumor infiltrating CD8

De Ponte Conti, Benedetta / Miluzio, Annarita / Grassi, Fabio / Abrignani, Sergio / Biffo, Stefano / Ricciardi, Sara

eLife

2021 Volume 10

Abstract: We performed a systematic analysis of the translation rate of tumor-infiltrating lymphocytes (TILs) and the microenvironment inputs affecting it, both in humans and in mice. Measurement of puromycin incorporation, a proxy of protein synthesis, revealed ... ...

Abstract	We performed a systematic analysis of the translation rate of tumor-infiltrating lymphocytes (TILs) and the microenvironment inputs affecting it, both in humans and in mice. Measurement of puromycin incorporation, a proxy of protein synthesis, revealed an increase of translating CD4
MeSH term(s)	CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Lymphocytes, Tumor-Infiltrating/metabolism ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	MTOR protein, human (EC 2.7.1.1) ; mTOR protein, mouse (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-11-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.69015
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Article ; Online: Exploring the links between cancer and placenta development.

Costanzo, Vincenzo / Bardelli, Alberto / Siena, Salvatore / Abrignani, Sergio

Open biology

2018 Volume 8, Issue 6

Abstract: The development of metastatic cancer is a multistage process, which often requires decades to complete. Impairments in DNA damage control and DNA repair in cancer cell precursors generate genetically heterogeneous cell populations. However, despite ... ...

Abstract	The development of metastatic cancer is a multistage process, which often requires decades to complete. Impairments in DNA damage control and DNA repair in cancer cell precursors generate genetically heterogeneous cell populations. However, despite heterogeneity most solid cancers have stereotypical behaviours, including invasiveness and suppression of immune responses that can be unleashed with immunotherapy targeting lymphocyte checkpoints. The mechanisms leading to the acquisition of stereotypical properties remain poorly understood. Reactivation of embryonic development processes in cells with unstable genomes might contribute to tumour expansion and metastasis formation. However, it is unclear whether these events are linked to immune response modulation. Tumours and embryos have non-self-components and need to avoid immune responses in their microenvironment. In mammalian embryos, neo-antigens are of paternal origin, while in tumour cells DNA mismatch repair and replication defects generate them. Inactivation of the maternal immune response towards the embryo, which occurs at the placental-maternal interface, is key to ensuring embryonic development. This regulation is accomplished by the trophoblast, which mimics several malignant cell features, including the ability to invade normal tissues and to avoid host immune responses, often adopting the same cancer immunoediting strategies. A better understanding as to whether and how genotoxic stress promotes cancer development through reactivation of programmes occurring during early stages of mammalian placentation could help to clarify resistance to drugs targeting immune checkpoint and DNA damage responses and to develop new therapeutic strategies to eradicate cancer.
MeSH term(s)	Animals ; Cellular Microenvironment ; Cellular Reprogramming ; Female ; Humans ; Neoplasms/immunology ; Placenta/embryology ; Placenta/immunology ; Placentation ; Pregnancy ; Trophoblasts/immunology
Language	English
Publishing date	2018-06-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2630944-0
ISSN	2046-2441 ; 2046-2441
ISSN (online)	2046-2441
ISSN	2046-2441
DOI	10.1098/rsob.180081
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Article ; Online: The endless frontier? The recent increase of R&D productivity in pharmaceuticals.

Pammolli, Fabio / Righetto, Lorenzo / Abrignani, Sergio / Pani, Luca / Pelicci, Pier Giuseppe / Rabosio, Emanuele

Journal of translational medicine

2020 Volume 18, Issue 1, Page(s) 162

Abstract: Background: Studies on the early 2000s documented increasing attrition rates and duration of clinical trials, leading to a representation of a "productivity crisis" in pharmaceutical research and development (R&D). In this paper, we produce a new set of ...

Abstract	Background: Studies on the early 2000s documented increasing attrition rates and duration of clinical trials, leading to a representation of a "productivity crisis" in pharmaceutical research and development (R&D). In this paper, we produce a new set of analyses for the last decade and report a recent increase of R&D productivity within the industry. Methods: We use an extensive data set on the development history of more than 50,000 projects between 1990 and 2017, which we integrate with data on sales, patents, and anagraphical information on each institution involved. We devise an indicator to quantify the novelty of each project, based on its set of mechanisms of action. Results: First, we investigate how R&D projects are allocated across therapeutic areas and find a polarization towards high uncertainty/high potential reward indications, with a strong focus on oncology. Second, we find that attrition rates have been decreasing at all stages of clinical research in recent years. In parallel, for each phase, we observe a significant reduction of time required to identify projects to be discontinued. Moreover, our analysis shows that more recent successful R&D projects are increasingly based on novel mechanisms of action and target novel indications, which are characterized by relatively small patient populations. Third, we find that the number of R&D projects on advanced therapies is also growing. Finally, we investigate the relative contribution to productivity variations of different types of institutions along the drug development process, with a specific focus on the distinction between the roles of Originators and Developers of R&D projects. We document that in the last decade Originator-Developer collaborations in which biotech companies act as Developers have been growing in importance. Moreover, we show that biotechnology companies have reached levels of productivity in project development that are equivalent to those of large pharmaceutical companies. Conclusions: Our study reports on the state of R&D productivity in the bio-pharmaceutical industry, finding several signals of an improving performance, with R&D projects becoming more targeted and novel in terms of indications and mechanisms of action.
MeSH term(s)	Drug Industry ; Humans ; Pharmaceutical Preparations ; Research
Chemical Substances	Pharmaceutical Preparations
Language	English
Publishing date	2020-04-09
Publishing country	England
Document type	Journal Article
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-020-02313-z
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Article ; Online: Eomesodermin-expressing type 1 regulatory (EOMES

Geginat, Jens / Vasco, Chiara / Gruarin, Paola / Bonnal, Raoul / Rossetti, Grazisa / Silvestri, Ylenia / Carelli, Elena / Pulvirenti, Nadia / Scantamburlo, Morena / Moschetti, Giorgia / Clemente, Francesca / Grassi, Fabio / Monticelli, Silvia / Pagani, Massimiliano / Abrignani, Sergio

European journal of immunology

2023 Volume 53, Issue 5, Page(s) e2149775

Abstract: Type 1 regulatory (Tr1) T cells are currently defined all T cells with regulatory functions that lack FOXP3 expression and produce IL-10. Tr1 cells are heterogeneous, and the different reported properties of Tr1-cell populations have caused some ... ...

Abstract	Type 1 regulatory (Tr1) T cells are currently defined all T cells with regulatory functions that lack FOXP3 expression and produce IL-10. Tr1 cells are heterogeneous, and the different reported properties of Tr1-cell populations have caused some confusion in the field. Moreover, understanding the role of Tr1 cells in immune-mediated diseases has been hampered by the lack of a lineage-defining transcription factor. Several independent studies indicated recently that the transcription factor Eomesodermin (EOMES) could act as a lineage-defining transcription factor in a population of IL-10 and IFN-γ co-producing Tr1-like cells, since EOMES directly induces IFN-γ and cytotoxicity, enhances IL-10, and antagonizes alternative T-cell fates. Here, we review the known properties of EOMES
MeSH term(s)	Interleukin-10/metabolism ; T-Lymphocytes, Regulatory ; Cell Differentiation ; Forkhead Transcription Factors/metabolism ; Biology
Chemical Substances	Interleukin-10 (130068-27-8) ; Forkhead Transcription Factors
Language	English
Publishing date	2023-03-17
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202149775
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