ORCID Profile
0000-0003-0040-3793
Current Organisations
Jawaharlal Nehru Medical College
,
University of Oxford Radcliffe Department of Medicine
,
University of Oxford
,
John Radcliffe Hospital
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Publications
Movie S3 from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543768.V1
Abstract: Movie S3 shows CD103- T cell killing HCT116 cancer cell, in brighfield imaging.
Movie S1 from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543774
Abstract: Movie S1 shows CD103+ T cell killing HCT116 cancer cell, in brighfield imaging.
Supplementary Fig S1-7, Sup Table 1 from Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8<sup>+</sup> Tumor-Infiltrating T Lymphocyte Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543995
Abstract: Supplementary Figure 1 to 7, Supplementary Table 1
Supplemental File For Publication from Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8<sup>+</sup> Tumor-Infiltrating T Lymphocyte Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543998
Abstract: Supplemental Figure Legends
Movie S1 from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543774.V1
Abstract: Movie S1 shows CD103+ T cell killing HCT116 cancer cell, in brighfield imaging.
Human T-Cell Leukemia Virus Type 1 Tax Protein Binds to Assembled Nuclear Proteasomes and Enhances Their Proteolytic Activity
Publisher: American Society for Microbiology
Date: 15-11-2001
DOI: 10.1128/JVI.75.22.11106-11115.2001
Abstract: The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates the HTLV-1 long terminal repeat and key regulatory proteins involved in inflammation, activation, and proliferation and may induce cell transformation. Tax is also the immunodominant target antigen for cytotoxic T cells in HTLV-1 infection. We found that Tax bound to assembled nuclear proteasomes, but Tax could not be detected in the cytoplasm. Confocal microscopy revealed a partial colocalization of Tax with nuclear proteasomes. As Tax translocated into the nucleus very quickly after synthesis, this process probably takes place prior to and independent of proteasome association. Tax mutants revealed that both the Tax N and C termini play a role in proteasome binding. We also found that proteasomes from Tax-transfected cells had enhanced proteolytic activity on prototypic peptide substrates. This effect was not due to the induction of the LMP2 and LMP7 proteasome subunits. Furthermore, Tax appeared to be a long-lived protein, with a half-life of around 15 h. These data suggest that the association of Tax with the proteasome and the enhanced proteolytic activity do not target Tax for rapid degradation and may not determine its immunodominance.
DOCK8 is critical for the survival and function of NKT cells
Publisher: American Society of Hematology
Date: 19-09-2013
DOI: 10.1182/BLOOD-2013-02-482331
Abstract: The development and survival of mature NKT cells are impaired in DOCK8-deficient mice. DOCK8 is required for antigen-induced NKT cell proliferation and cytokine production.
Surface Expression of HLA-E, an Inhibitor of Natural Killer Cells, Enhanced by Human Cytomegalovirus gpUL40
Publisher: American Association for the Advancement of Science (AAAS)
Date: 11-02-2000
DOI: 10.1126/SCIENCE.287.5455.1031
Abstract: The nonclassical major histocompatibility complex (MHC) class I molecule HLA-E inhibits natural killer (NK) cell–mediated lysis by interacting with CD94/NKG2A receptors. Surface expression of HLA-E depends on binding of conserved peptides derived from MHC class I molecules. The same peptide is present in the leader sequence of the human cytomegalovirus (HCMV) glycoprotein UL40 (gpUL40). It is shown that, independently of the transporter associated with antigen processing, gpUL40 can up-regulate expression of HLA-E, which protects targets from NK cell lysis. While classical MHC class I molecules are down-regulated, HLA-E is up-regulated by HCMV. Induction of HLA-E surface expression by gpUL40 may represent an escape route for HCMV.
Movie S2 from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543771
Abstract: Movie S2 shows CD103+ T cell killing HCT116 cancer cell, by calcium flux imaging.
Supplementary Fig S1-7, Sup Table 1 from Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8<sup>+</sup> Tumor-Infiltrating T Lymphocyte Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543995.V1
Abstract: Supplementary Figure 1 to 7, Supplementary Table 1
Cord Factor and Peptidoglycan Recapitulate the Th17-Promoting Adjuvant Activity of Mycobacteria through Mincle/CARD9 Signaling and the Inflammasome
Publisher: The American Association of Immunologists
Date: 06-2013
Abstract: Although adjuvants are critical vaccine components, their modes of action are poorly understood. In this study, we investigated the mechanisms by which the heat-killed mycobacteria in CFA promote Th17 CD4+ T cell responses. We found that IL-17 secretion by CD4+ T cells following CFA immunization requires MyD88 and IL-1β/IL-1R signaling. Through measurement of Ag-specific responses after adoptive transfer of OTII cells, we confirmed that MyD88-dependent signaling controls Th17 differentiation rather than simply production of IL-17. Additional experiments showed that CFA-induced Th17 differentiation involves IL-1β processing by the inflammasome, as mice lacking caspase-1, ASC, or NLRP3 exhibit partially defective responses after immunization. Biochemical fractionation studies further revealed that peptidoglycan is the major component of heat-killed mycobacteria responsible for inflammasome activation. By assaying Il1b transcripts in the injection site skin of CFA-immunized mice, we found that signaling through the adaptor molecule caspase activation and recruitment domain 9 (CARD9) plays a major role in triggering pro–IL-1β expression. Moreover, we demonstrated that recognition of the mycobacterial glycolipid trehalose dimycolate (cord factor) by the C-type lectin receptor mincle partially explains this CARD9 requirement. Importantly, purified peptidoglycan and cord factor administered in mineral oil synergized to recapitulate the Th17-promoting activity of CFA, and, as expected, this response was diminished in caspase-1– and CARD9-deficient mice. Taken together, these findings suggest a general strategy for the rational design of Th17-skewing adjuvants by combining agonists of the CARD9 pathway with inflammasome activators.
Data from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.C.6550399
Abstract: Abstract Enrichment of CD103 sup + /sup tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103 sup + /sup cytotoxic CD8 sup + /sup T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103 sup + /sup CTLs by assessing T-cell receptor (TCR)–matched CD103 sup + /sup and CD103 sup − /sup cancer-specific CTL immunity i in vitro /i and its immunophenotype i ex vivo /i . Interestingly, we found that differentiated CD103 sup + /sup cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103 sup + /sup CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103 sup + /sup cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies. /
Data from Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8<sup>+</sup> Tumor-Infiltrating T Lymphocyte Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.C.6550497
Abstract: Abstract Immunotherapy treatments with anti-PD-1 boost recovery in less than 30% of treated cancer patients, indicating the complexity of the tumor microenvironment. Expression of HLA-E is linked to poor clinical outcomes in mice and human patients. However, the contributions to immune evasion of HLA-E, a ligand for the inhibitory CD94/NKG2A receptor, when expressed on tumors, compared with adjacent tissue and peripheral blood mononuclear cells, remains unclear. In this study, we report that epithelial-derived cancer cells, tumor macrophages, and CD141 sup + /sup conventional dendritic cells (cDC) contributed to HLA-E enrichment in carcinomas. Different cancer types showed a similar pattern of enrichment. Enrichment correlated to NKG2A upregulation on CD8 sup + /sup tumor-infiltrating T lymphocytes (TIL) but not on CD4 sup + /sup TILs. CD94/NKG2A is exclusively expressed on PD-1 sup high /sup TILs while lacking intratumoral CD103 expression. We also found that the presence of CD94/NKG2A on human tumor–specific T cells impairs IL2 receptor–dependent proliferation, which affects IFNγ-mediated responses and antitumor cytotoxicity. These functionalities recover following antibody-mediated blockade i in vitro /i and i ex vivo /i . Our results suggest that enriched HLA-E:CD94/NKG2A inhibitory interaction can impair survival of PD-1 sup high /sup TILs in the tumor microenvironment. /
Supplementary Movie Titles and Legends from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543759
Abstract: Titles and Legends for Movies 1-4
Determinants of Intimate Partner Violence Among HIV-Positive and HIV-Negative Women in India
Publisher: SAGE Publications
Date: 06-11-2014
Abstract: To reduce the many adverse health outcomes associated with intimate partner violence (IPV), high-risk groups need to be specifically targeted in the fight against domestic violence in India. This study aims to examine the prevalence and correlates of IPV in HIV-positive and HIV-negative women from India. A convenience s le of HIV-positive and HIV-negative women responded to questionnaires to assess their experience and perception of violence. Multivariate logistic regression analysis was used to model the association between IPV and age, education, employment status, contraception use, age at first marriage, and HIV status. Although adjusting for age, education, employment status, contraception use, age at first marriage, and HIV status, women who are employed were 3.5 times more likely to suffer IPV (confidence interval [CI] = [1.5, 8.5]), women aged 18 or above at first marriage are 0.3 times less likely to face IPV (CI = [0.1, 0.6]), and women who use contraception are 7 times more likely to suffer IPV (CI = [1.4, 30.2]). Also, HIV-positive women are 3 times more likely to face sexual violence compared with HIV-negative women (CI = [1.1, 7.6]).
Supplementary Figures 1-7 and Supplementary Tables 1-2 from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543762
Abstract: Supplementary Figures and Tables
Movie S4 from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543765
Abstract: Movie S4 shows CD103- T cell killing HCT116 cancer cell, by calcium flux imaging.
Data from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.C.6550399.V1
Abstract: Abstract Enrichment of CD103 sup + /sup tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103 sup + /sup cytotoxic CD8 sup + /sup T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103 sup + /sup CTLs by assessing T-cell receptor (TCR)–matched CD103 sup + /sup and CD103 sup − /sup cancer-specific CTL immunity i in vitro /i and its immunophenotype i ex vivo /i . Interestingly, we found that differentiated CD103 sup + /sup cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103 sup + /sup CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103 sup + /sup cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies. /
Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8+ Tumor-Infiltrating T Lymphocyte Responses
Publisher: American Association for Cancer Research (AACR)
Date: 08-2019
DOI: 10.1158/2326-6066.CIR-18-0885
Abstract: Immunotherapy treatments with anti-PD-1 boost recovery in less than 30% of treated cancer patients, indicating the complexity of the tumor microenvironment. Expression of HLA-E is linked to poor clinical outcomes in mice and human patients. However, the contributions to immune evasion of HLA-E, a ligand for the inhibitory CD94/NKG2A receptor, when expressed on tumors, compared with adjacent tissue and peripheral blood mononuclear cells, remains unclear. In this study, we report that epithelial-derived cancer cells, tumor macrophages, and CD141+ conventional dendritic cells (cDC) contributed to HLA-E enrichment in carcinomas. Different cancer types showed a similar pattern of enrichment. Enrichment correlated to NKG2A upregulation on CD8+ tumor-infiltrating T lymphocytes (TIL) but not on CD4+ TILs. CD94/NKG2A is exclusively expressed on PD-1high TILs while lacking intratumoral CD103 expression. We also found that the presence of CD94/NKG2A on human tumor–specific T cells impairs IL2 receptor–dependent proliferation, which affects IFNγ-mediated responses and antitumor cytotoxicity. These functionalities recover following antibody-mediated blockade in vitro and ex vivo. Our results suggest that enriched HLA-E:CD94/NKG2A inhibitory interaction can impair survival of PD-1high TILs in the tumor microenvironment.
Movie S4 from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543765.V1
Abstract: Movie S4 shows CD103- T cell killing HCT116 cancer cell, by calcium flux imaging.
Respiratory infections drive hepcidin-mediated blockade of iron absorption leading to iron deficiency anemia in African children
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-2019
Abstract: Inflammation from respiratory infections contributes to iron deficiency anemia in children by blocking iron absorption.
Publisher Correction: Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses.
Publisher: Springer Science and Business Media LLC
Date: 12-03-2019
DOI: 10.1038/S41590-019-0357-6
Abstract: In the version of this article initially published, the first affiliation lacked 'MRC' the correct name of the institution is 'MRC Weatherall Institute of Molecular Medicine'. Two designations (SP110Y and ST110H) were incorrect in the legend to Fig. 6f,h,i. The correct text is as follows: for panel f, "...loaded with either the CdtB(105-125)SP110Y (DRB4*SP110Y) or the CdtB(105-125)ST110H (DRB4*ST110H) peptide variants..." for panel h, "...decorated by the DRB4*SP110Y tetramer (lower-right quadrant), the DRB4*ST110H (upper-left quadrant)..." and for panel i, "...stained ex vivo with DRB4*SP110Y, DRB4*ST110H...". In Fig. 8e, the final six residues (LTEAFF) of the sequence in the far right column of the third row of the table were missing the correct sequence is 'CASSYRRTPPLTEAFF'. In the legend to Fig. 8d, a designation (HLyE) was incorrect the correct text is as follows: "(HlyE?)." Portions of the Acknowledgements section were incorrect the correct text is as follows: "This work was supported by the UK Medical Research Council (MRC) (MR/K021222/1) (G.N., M.A.G., A.S., V.C., A.J.P.),...the Oxford Biomedical Research Centre (A.J.P., V.C.),...and core funding from the Singapore Immunology Network (SIgN) (E.W.N.) and the SIgN immunomonitoring platform (E.W.N.)." Finally, a parenthetical element was phrased incorrectly in the final paragraph of the Methods subsection "T cell cloning and live fluorescence barcoding" the correct phrasing is as follows: "...(which in all cases included HlyE, CdtB, Ty21a, Quailes, NVGH308, and LT2 strains and in volunteers T5 and T6 included PhoN)...". Also, in Figs. 3c and 4a, the right outlines of the plots were not visible in the legend to Fig. 3, panel letter 'f' was not bold and in Fig. 8f, 'ND' should be aligned directly beneath DRB4 in the key and 'ND' should be removed from the diagram at right, and the legend should be revised accordingly as follows: "...colors indicate the HLA class II restriction (gray indicates clones for which restriction was not determined (ND)). Clonotypes are grouped on the basis of pathogen selectivity (continuous line), protein specificity (dashed line) and epitope specificity for ten HlyE-specific clones (pixilated squares), the epitope specificity was not determined...". The errors have been corrected in the HTML and PDF versions of the article.
Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria
Publisher: Rockefeller University Press
Date: 25-02-2019
DOI: 10.1084/JEM.20181812
Abstract: Salmonella species are among the world’s most prevalent pathogens. Because the cell wall interfaces with the host, we designed a lipidomics approach to reveal pathogen-specific cell wall compounds. Among the molecules differentially expressed between Salmonella Paratyphi and S. Typhi, we focused on lipids that are enriched in S. Typhi, because it causes typhoid fever. We discovered a previously unknown family of trehalose phospholipids, 6,6′-diphosphatidyltrehalose (diPT) and 6-phosphatidyltrehalose (PT). Cardiolipin synthase B (ClsB) is essential for PT and diPT but not for cardiolipin biosynthesis. Chemotyping outperformed clsB homology analysis in evaluating synthesis of diPT. DiPT is restricted to a subset of Gram-negative bacteria: large amounts are produced by S. Typhi, lower amounts by other pathogens, and variable amounts by Escherichia coli strains. DiPT activates Mincle, a macrophage activating receptor that also recognizes mycobacterial cord factor (6,6′-trehalose dimycolate). Thus, Gram-negative bacteria show convergent function with mycobacteria. Overall, we discovered a previously unknown immunostimulant that is selectively expressed among medically important bacterial species.
Movie S2 from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543771.V1
Abstract: Movie S2 shows CD103+ T cell killing HCT116 cancer cell, by calcium flux imaging.
Factors influencing participation in controlled human infection models: a pooled analysis from six enteric fever studies
Publisher: F1000 Research Ltd
Date: 11-10-2019
DOI: 10.12688/WELLCOMEOPENRES.15469.1
Abstract: Background: Enteric fever is an acute febrile-illness caused by infection with the human-restricted Salmonella serovars Typhi and Paratyphi. Controlled human infection models (CHIM) of S . Typhi and Paratyphi infection are used to accelerate vaccine development and to better understand host-pathogen interactions. The primary motivations for participants to take part in these studies are unknown. We studied participant motivations, attitudes and the factors influencing CHIM study participation. Methods: Participant surveys were nested in six enteric fever CHIM studies conducted at a single centre in Oxford, UK, between 2011 and 2017. All eligible participants received one invitation to complete an anonymous, self-administered paper or online survey on either day 28 or 60 after challenge. A descriptive analysis was performed on these pooled data. All studies were included, to minimize selection bias. Results: Survey response rates varied from 33.0%-86.1%, yielding 201 participants. In the cohort, 113/198(57.0%) were educated to bachelor’s level, 61.6% were employed, 30.3% were students and 4.6% were unemployed. The most commonly cited motivations for CHIM study participation were a desire to contribute to the progression of medicine (170/201 84.6%) the prospect of financial reimbursement (166/201 82.6%) and curiosity about clinical trials (117/201 57.2%). The majority of respondents (139/197 70.6%) reported that most people advised them against participation. Conclusion: Motivation to participate in a CHIM study was multi-factorial and heavily influenced by internal drivers beyond monetary reimbursement alone. High educational attainment and employment may be protective factors against financial inducement however, further research is needed, particularly with CHIM studies expanding to low-income and middle-income countries.
Movie S3 from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543768
Abstract: Movie S3 shows CD103- T cell killing HCT116 cancer cell, in brighfield imaging.
Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 02-2020
DOI: 10.1158/2326-6066.CIR-19-0554
Abstract: Enrichment of CD103+ tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103+ cytotoxic CD8+ T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103+ CTLs by assessing T-cell receptor (TCR)–matched CD103+ and CD103− cancer-specific CTL immunity in vitro and its immunophenotype ex vivo. Interestingly, we found that differentiated CD103+ cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103+ CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103+ cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies.
Treatment responses to Azithromycin and Ciprofloxacin in uncomplicated Salmonella Typhi infection: A comparison of Clinical and Microbiological Data from a Controlled Human Infection Model
Publisher: Public Library of Science (PLoS)
Date: 26-12-2019
Supplemental File For Publication from Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8<sup>+</sup> Tumor-Infiltrating T Lymphocyte Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543998.V1
Abstract: Supplemental Figure Legends
Supplementary Movie Titles and Legends from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543759.V1
Abstract: Titles and Legends for Movies 1-4
T Cell Receptor CDR2β and CDR3β Loops Collaborate Functionally to Shape the iNKT Cell Repertoire
Publisher: Elsevier BV
Date: 07-2009
Frequency and Phenotype of Circulating Vα24/Vβ11 Double-Positive Natural Killer T Cells during Hepatitis C Virus Infection
Publisher: American Society for Microbiology
Date: 02-2003
DOI: 10.1128/JVI.77.3.2251-2257.2003
Abstract: Natural killer T (NKT) cells are thought to be involved in innate responses against infection. We investigated one specific type of NKT cell, Vα24/Vβ11 double positive, in hepatitis C virus (HCV) infection. Lower frequencies of this population were detected in the blood of HCV PCR-positive patients than in controls. Unlike Vα24/Vβ11 NKT cells found in blood, those in the liver appeared to be recently activated.
Supplementary Figures 1-7 and Supplementary Tables 1-2 from Self-Maintaining CD103<sup>+</sup> Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.22543762.V1
Abstract: Supplementary Figures and Tables
Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses
Publisher: Springer Science and Business Media LLC
Date: 27-11-2012
DOI: 10.1038/NI.2166
Abstract: Lipid antigens trigger help from natural killer T cells (NKT cells) for B cells, and direct conjugation of lipid agonists to antigen profoundly augments antibody responses. Here we show that in vivo, NKT cells engaged in stable and prolonged cognate interactions with B cells and induced the formation of early germinal centers. Mouse and human NKT cells formed CXCR5(+)PD-1(hi) follicular helper NKT cells (NKT(FH) cells), and this process required expression of the transcriptional repressor Bcl-6, signaling via the coreceptor CD28 and interaction with B cells. NKT(FH) cells provided direct cognate help to antigen-specific B cells that was dependent on interleukin 21 (IL-21). Unlike T cell-dependent germinal centers, those driven by NKT(FH) cells did not generate long-lived plasma cells. Our results demonstrate the existence of a Bcl-6-dependent subset of NKT cells specialized in providing help to B cells.
Data from Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8<sup>+</sup> Tumor-Infiltrating T Lymphocyte Responses
Publisher: American Association for Cancer Research (AACR)
Date: 04-04-2023
DOI: 10.1158/2326-6066.C.6550497.V1
Abstract: Abstract Immunotherapy treatments with anti-PD-1 boost recovery in less than 30% of treated cancer patients, indicating the complexity of the tumor microenvironment. Expression of HLA-E is linked to poor clinical outcomes in mice and human patients. However, the contributions to immune evasion of HLA-E, a ligand for the inhibitory CD94/NKG2A receptor, when expressed on tumors, compared with adjacent tissue and peripheral blood mononuclear cells, remains unclear. In this study, we report that epithelial-derived cancer cells, tumor macrophages, and CD141 sup + /sup conventional dendritic cells (cDC) contributed to HLA-E enrichment in carcinomas. Different cancer types showed a similar pattern of enrichment. Enrichment correlated to NKG2A upregulation on CD8 sup + /sup tumor-infiltrating T lymphocytes (TIL) but not on CD4 sup + /sup TILs. CD94/NKG2A is exclusively expressed on PD-1 sup high /sup TILs while lacking intratumoral CD103 expression. We also found that the presence of CD94/NKG2A on human tumor–specific T cells impairs IL2 receptor–dependent proliferation, which affects IFNγ-mediated responses and antitumor cytotoxicity. These functionalities recover following antibody-mediated blockade i in vitro /i and i ex vivo /i . Our results suggest that enriched HLA-E:CD94/NKG2A inhibitory interaction can impair survival of PD-1 sup high /sup TILs in the tumor microenvironment. /
Related Organisations
University Of Oxford Radcliffe Department Of Medicine
Location: United Kingdom of Great Britain and Northern Ireland
Università Degli Studi Di Padova Facoltà Di Medicina E Chirurgia
Location: Italy
Medical Research Council
Location: United Kingdom of Great Britain and Northern Ireland
University Of Oxford
Location: United Kingdom of Great Britain and Northern Ireland
John Radcliffe Hospital
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Vincenzo Cerundolo.