Clinical & Translational Immunology最新文献

{"title":"Individualised adjuvant immunotherapy with neoantigen-reactive T cells for gastric signet-ring cell carcinoma","authors":"Naiqing Ding,&nbsp;Qin Liu,&nbsp;Juan Du,&nbsp;Jie Shao,&nbsp;Yang Yang,&nbsp;Ju Yang,&nbsp;Fangjun Chen,&nbsp;Lixia Yu,&nbsp;Baorui Liu,&nbsp;Jia Wei","doi":"10.1002/cti2.1467","DOIUrl":"10.1002/cti2.1467","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The signet-ring cell carcinoma (SRCC) of the stomach is highly invasive. Patients with stage III gastric SRCC usually experience tumor recurrence within 2 years after radical surgery. Unfortunately, there is no effective treatment to postpone recurrence following adjuvant chemotherapy. Our study aimed to explore the safety and efficacy of neoantigen-reactive T lymphocytes (NRTs) in patients with stage III gastric SRCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 20 patients with stage III gastric SRCC who received radical surgery and adjuvant chemotherapy. Following the adjuvant chemotherapy, they underwent treatment with a range of one to four cycles of personalised neoantigen-reactive T cells. The primary endpoint was the median progression-free survival (mDFS). The secondary endpoint was safety and immune responses. The median duration of follow-up was 41 months (95% CI: 39–42.9 months).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results showed that patients who received adjuvant neoantigen-reactive T-cell immunotherapy demonstrated a propensity towards prolonged disease-free survival (DFS) and overall survival (OS) in comparison to previous studies. The 2-year DFS and OS rates reached 73.7% and 95%, respectively, whereas the 5-year DFS and OS rates were 44% and 69%. The median DFS was 41 months (95% CI: 28.9–53.1 months) and the median OS was not reached. In addition, there was a significant increase in serum concentrations of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ after cell immunotherapy. The adverse reactions were mild.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, adjuvant immunotherapy with NRTs showed promising efficacy alongside a manageable safety profile.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 9","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/15/65/CTI2-12-e1467.PMC10494288.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10229893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, optimisation and standardisation of a high-dimensional spectral flow cytometry workflow assessing T-cell immunophenotype in patients with melanoma","authors":"Jack M Edwards,&nbsp;Miles C Andrews,&nbsp;Hayley Burridge,&nbsp;Robin Smith,&nbsp;Carole Owens,&nbsp;Mark Edinger,&nbsp;Katherine Pilkington,&nbsp;Juliette Desfrancois,&nbsp;Mark Shackleton,&nbsp;Sashendra Senthi,&nbsp;Menno C van Zelm","doi":"10.1002/cti2.1466","DOIUrl":"https://doi.org/10.1002/cti2.1466","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Despite the success of immune checkpoint blockade, most metastatic melanoma patients fail to respond to therapy or experience severe toxicity. Assessment of biomarkers and immunophenotypes before or early into treatment will help to understand favourable responses and improve therapeutic outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We present a high-dimensional approach for blood T-cell profiling using three multi-parameter cytometry panels: (1) a TruCount panel for absolute cell counts, (2) a 27-colour spectral panel assessing T-cell markers and (3) a 20-colour spectral panel evaluating intracellular cytokine expression. Pre-treatment blood mononuclear cells from patients and healthy controls were cryopreserved before staining across 11 batches. Batch effects were tracked using a single-donor control and the suitability of normalisation was assessed. The data were analysed using manual gating and high-dimensional strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Batch-to-batch variation was minimal, as demonstrated by the dimensionality reduction of batch-control samples, and normalisation did not improve manual or high-dimensional analysis. Application of the workflow demonstrated the capacity of the panels and showed that patients had fewer lymphocytes than controls (<i>P</i> = 0.0027), due to lower naive CD4⁺ (<i>P</i> = 0.015) and CD8⁺ (<i>P</i> = 0.011) T cells and follicular helper T cells (<i>P</i> = 0.00076). Patients showed trends for higher proportions of Ki67 and IL-2-expressing cells within CD4⁺ and CD8⁺ memory subsets, and increased CD57 and EOMES expression within TCRγδ⁺ T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our optimised high-parameter spectral cytometry approach provided in-depth profiling of blood T cells and found differences in patient immunophenotype at baseline. The robustness of our workflow, as demonstrated by minimal batch effects, makes this approach highly suitable for the longitudinal evaluation of immunotherapy effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 9","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6303019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic and tumour microenvironmental biomarkers of immune checkpoint inhibitor response in advanced Taiwanese melanoma","authors":"John Wen-Cheng Chang,&nbsp;Chien-Jung Huang,&nbsp;Wen-Kuan Huang,&nbsp;Yu-Chao Wang,&nbsp;Jia-Juan Hsieh,&nbsp;Yao-Yu Chang,&nbsp;Yen-Lin Huang,&nbsp;Chia-Ling Wu,&nbsp;Yeh-Han Wang,&nbsp;Shu-Jen Chen,&nbsp;Kien Thiam Tan,&nbsp;Chiao-Ping Chen,&nbsp;Chiao-En Wu","doi":"10.1002/cti2.1465","DOIUrl":"10.1002/cti2.1465","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Genomic biomarkers predicting immune checkpoint inhibitor (ICI) treatment outcomes for Asian metastatic melanoma have been rarely reported. This study presents data on next-generation sequencing (NGS) and tumour microenvironment biomarkers in 33 cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-three patients with advanced melanoma, who underwent ICI treatment at the Chang Gung Memorial Hospital in Taiwan, were recruited. The study evaluated clinical outcomes, including response rate, disease control rate, progression-free survival (PFS) rate and overall survival (OS) rate. Archived tissue samples from 33 cases were subjected to NGS by ACTOnco, and ACTTME was employed in 25 cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The most prevalent driver mutations were <i>BRAF</i> mutations (24.2%), followed by <i>NRAS</i> (15.2%), <i>KIT</i> (12.1%), <i>KRAS</i> (9.1%) and <i>NF1</i> (9.1%) mutations. Acral/mucosal melanomas exhibited distinct mutation patterns compared to non-acral melanomas. Tumour mutational burden estimated using ACTOnco was not associated with ICI efficacy. Notably, genetic alterations in the p53 pathway (<i>CDKNA2</i> loss, <i>MDM2</i> gain/amplification and <i>TP53</i> mutation) accounted for 36.4% and were significantly associated with unfavourable PFS (median PFS 2.7 months <i>vs.</i> 3.9 months, <i>P =</i> 0.0394). Moreover, 26 genes were identified as differentially expressed genes that were upregulated in patients with clinical benefits compared to those without benefits. Four genes, <i>GZMH</i>, <i>GZMK</i>, <i>AIM2</i> and <i>CTLA4</i>, were found to be associated with both PFS and OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Genetic alterations in the p53 pathway may be critical in Asian patients with melanoma undergoing ICI treatment. Further investigation is required to explore this mechanism and validate these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 8","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/ae/CTI2-12-e1465.PMC10463562.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10118760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoid regulation of the mTORC1 pathway modulates CD4+ T cell responses during infection","authors":"Huihui Chen,&nbsp;Zhiwen Liu,&nbsp;Jie Zha,&nbsp;Li Zeng,&nbsp;Runyan Tang,&nbsp;Chengyuan Tang,&nbsp;Juan Cai,&nbsp;Chongqing Tan,&nbsp;Hong Liu,&nbsp;Zheng Dong,&nbsp;Guochun Chen","doi":"10.1002/cti2.1464","DOIUrl":"10.1002/cti2.1464","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Conventional glucocorticoid (GC) treatment poses significant risks for opportunistic infections due to its suppressive impact on CD4⁺ T cells. This study aimed to explore the mechanisms by which GCs modulate the functionality of CD4⁺ T cells during infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We consistently measured FOXP3, inflammatory cytokines and phospho-S6 ribosomal protein levels in CD4⁺ T cells from patients undergoing conventional GC treatment. Using Foxp3^EGFP animals, we investigated the dynamic activation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway and its correlation with the immunoregulatory function of CD4⁺ T cells under the influence of GCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GCs dynamically altered the expression pattern of FOXP3 in CD4⁺ T cells, promoting their acquisition of an active T regulatory (Treg) cell phenotype upon stimulation. Mechanistically, GCs undermined the kinetics of the mTORC1 pathway, which was closely correlated with phenotype conversion and functional properties of CD4⁺ T cells. Dynamic activation of the mTORC1 signaling modified the GC-dampened immunoregulatory capacity of CD4⁺ T cells by phenotypically and functionally bolstering the FOXP3⁺ Treg cells. Interventions targeting the mTORC1 pathway effectively modulated the GC-dampened immunoregulatory capacity of CD4⁺ T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight a novel mTORC1-mediated mechanism underlying CD4⁺ T cell immunity in the context of conventional GC treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 8","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/da/CTI2-12-e1464.PMC10463561.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10125547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A unique cytotoxic CD4+ T cell-signature defines critical COVID-19","authors":"Sarah Baird,&nbsp;Caroline L Ashley,&nbsp;Felix Marsh-Wakefield,&nbsp;Sibel Alca,&nbsp;Thomas M Ashhurst,&nbsp;Angela L Ferguson,&nbsp;Hannah Lukeman,&nbsp;Claudio Counoupas,&nbsp;Jeffrey J Post,&nbsp;Pamela Konecny,&nbsp;Adam Bartlett,&nbsp;Marianne Martinello,&nbsp;Rowena A Bull,&nbsp;Andrew Lloyd,&nbsp;Alice Grey,&nbsp;Owen Hutchings,&nbsp;Umaimainthan Palendira,&nbsp;Warwick J Britton,&nbsp;Megan Steain,&nbsp;James A Triccas","doi":"10.1002/cti2.1463","DOIUrl":"10.1002/cti2.1463","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>SARS-CoV-2 infection causes a spectrum of clinical disease presentation, ranging from asymptomatic to fatal. While neutralising antibody (NAb) responses correlate with protection against symptomatic and severe infection, the contribution of the T-cell response to disease resolution or progression is still unclear. As newly emerging variants of concern have the capacity to partially escape NAb responses, defining the contribution of individual T-cell subsets to disease outcome is imperative to inform the development of next-generation COVID-19 vaccines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Immunophenotyping of T-cell responses in unvaccinated individuals was performed, representing the full spectrum of COVID-19 clinical presentation. Computational and manual analyses were used to identify T-cell populations associated with distinct disease states.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Critical SARS-CoV-2 infection was characterised by an increase in activated and cytotoxic CD4⁺ lymphocytes (CTL). These CD4⁺ CTLs were largely absent in asymptomatic to severe disease states. In contrast, non-critical COVID-19 was associated with high frequencies of naïve T cells and lack of activation marker expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Highly activated and cytotoxic CD4⁺ T-cell responses may contribute to cell-mediated host tissue damage and progression of COVID-19. Induction of these potentially detrimental T-cell responses should be considered when developing and implementing effective COVID-19 control strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 8","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/2f/CTI2-12-e1463.PMC10461786.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10307651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of antibodies in the upper and lower human respiratory tract at steady state and after respiratory viral infection","authors":"Marios Koutsakos,&nbsp;Jackson S Turner,&nbsp;M Cristina Vazquez Guillamet,&nbsp;Daniel Reynolds,&nbsp;Tingting Lei,&nbsp;Derek E Byers,&nbsp;Ali H Ellebedy,&nbsp;Philip A Mudd","doi":"10.1002/cti2.1460","DOIUrl":"https://doi.org/10.1002/cti2.1460","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>There is an increasing appreciation for the need to study mucosal antibody responses in humans. Our aim was to determine the utility of different types of samples from the human respiratory tract, specifically nasopharyngeal (NP) swabs obtained for diagnostic purposes and bronchoalveolar lavage (BAL) obtained in outpatient and inpatient settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed antibody levels in plasma and NP swabs from 67 individuals with acute influenza as well as plasma and BAL from individuals undergoing bronchoscopy, including five control subjects as well as seven moderately and seven severely ill subjects with a respiratory viral infection. Levels of α2-macroglobulin were determined in BAL and plasma to assess plasma exudation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IgG and IgA were readily detectable in BAL and NP swabs, albeit at different ratios, while IgM levels were low. The total amount of antibody recovered from NP swabs varied greatly between study participants. Accordingly, the levels of influenza HA-specific antibodies varied, and individuals with lower amounts of total Ig in NP swabs had undetectable levels of HA-specific Ig. Similarly, the total amount of antibody recovered from BAL varied between study participants. However, severely ill patients showed evidence of increased plasma exudation, which may confound analysis of their BAL samples for mucosal antibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Nasopharyngeal swabs collected for diagnostic purposes may have utility in assessing antibodies from the human nasal mucosa, but variability in sampling should be accounted for. BAL samples can be utilised to study antibodies from the lower respiratory tract, but the possibility of plasma exudation should be excluded.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 8","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6183924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD-L1) expression in colorectal carcinoma","authors":"Tomotaka Ugai,&nbsp;Takashi Shimizu,&nbsp;Hidetaka Kawamura,&nbsp;Satoko Ugai,&nbsp;Yasutoshi Takashima,&nbsp;Genki Usui,&nbsp;Juha P V?yrynen,&nbsp;Kazuo Okadome,&nbsp;Koichiro Haruki,&nbsp;Naohiko Akimoto,&nbsp;Yohei Masugi,&nbsp;Annacarolina da Silva,&nbsp;Kosuke Mima,&nbsp;Xuehong Zhang,&nbsp;Andrew T Chan,&nbsp;Molin Wang,&nbsp;Wendy S Garrett,&nbsp;Gordon J Freeman,&nbsp;Jeffrey A Meyerhardt,&nbsp;Jonathan A Nowak,&nbsp;Mingyang Song,&nbsp;Marios Giannakis,&nbsp;Shuji Ogino","doi":"10.1002/cti2.1453","DOIUrl":"https://doi.org/10.1002/cti2.1453","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of <i>Fusobacterium nucleatum</i>. We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of <i>F. nucleatum</i> in colorectal carcinoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed tumor CD274 expression by immunohistochemistry and <i>F. nucleatum</i> DNA within tumor tissue by quantitative PCR in 812 cases among 4465 incident rectal and colon cancer cases that had occurred in two prospective cohort studies. Multivariable logistic regression analyses with inverse probability weighting were used to adjust for selection bias because of tissue data availability and potential confounders including microsatellite instability status, CpG island methylator phenotype, LINE-1 methylation level and <i>KRAS</i>, <i>BRAF</i> and <i>PIK3CA</i> mutations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>Fusobacterium nucleatum</i> DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of <i>F. nucleatum</i> in colorectal cancer tissue (<i>P</i> = 0.0077). For one category-unit increase in three ordinal <i>F. nucleatum</i> categories (negative vs. low vs. high), multivariable-adjusted odds ratios (with 95% confidence interval) of the low, intermediate and high CD274 categories (vs. negative) were 0.78 (0.41–1.51), 0.64 (0.32–1.28) and 0.50 (0.25–0.99), respectively (<i>P</i>_trend = 0.032).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Tumor CD274 expression level was inversely associated with the amount of <i>F. nucleatum</i> in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor <i>F. nucleatum</i> enrichment) tend to be used by different tumor subgroups.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 8","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1453","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6083231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case of T-cell-Epstein–Barr virus-haemophagocytic lymphohistiocytosis and sustained remission following ruxolitinib therapy","authors":"Syed Ali,&nbsp;Sharon Choo,&nbsp;Laine Hosking,&nbsp;Anthony Smith,&nbsp;Tiffany Hughes","doi":"10.1002/cti2.1459","DOIUrl":"https://doi.org/10.1002/cti2.1459","url":null,"abstract":"Epstein–Barr virus (EBV) is a common cause of secondary haemophagocytic lymphohistiocytosis (HLH). While B cells are reservoirs for EBV, infection within T cells and NK cells in this disease can be difficult to treat.","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 7","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5803734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic haematopoietic cell transplants as dynamical systems: influence of early-term immune milieu on long-term T-cell recovery","authors":"Viktoriya Zelikson,&nbsp;Roy Sabo,&nbsp;Myrna Serrano,&nbsp;Younus Aqeel,&nbsp;Savannah Ward,&nbsp;Taha Al Juhaishi,&nbsp;May Aziz,&nbsp;Elizabeth Krieger,&nbsp;Gary Simmons,&nbsp;Catherine Roberts,&nbsp;Jason Reed,&nbsp;Gregory Buck,&nbsp;Amir Toor","doi":"10.1002/cti2.1458","DOIUrl":"https://doi.org/10.1002/cti2.1458","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Immune recovery following haematopoietic cell transplantation (HCT) functions as a dynamical system. Reducing the duration of intense immune suppression and augmenting antigen presentation has the potential to optimise T-cell reconstitution, potentially influencing long-term outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Based on donor-derived T-cell recovery, 26 patients were adaptively randomised between mycophenolate mofetil (MMF) administered for 30-day post-transplant with filgrastim for cytokine support (MMF30 arm, <i>N</i> = 11), or MMF given for 15 days with sargramostim (MMF15 arm, <i>N</i> = 15). All patients underwent <i>in vivo</i> T-cell depletion with 5.1 mg kg⁻¹ antithymocyte globulin (administered over 3 days, Day −9 through to Day −7) and received reduced intensity 450 cGy total body irradiation (3 fractions on Day −1 and Day 0). Patients underwent HLA-matched related and unrelated donor haematopoietic cell transplantation (HCT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Clinical outcomes were equivalent between the two groups. The MMF15 arm demonstrated superior T-cell, as well as T-cell subset recovery and a trend towards superior T-cell receptor (TCR) diversity in the first month with this difference persisting through the first year. T-cell repertoire recovery was more rapid and sustained, as well as more diverse in the MMF15 arm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The long-term superior immune recovery in the MMF15 arm, administered GMCSF, is consistent with a disproportionate impact of early interventions in HCT. Modifying the ‘immune-milieu’ following allogeneic HCT is feasible and may influence long-term T-cell recovery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 7","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5839002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robust immunity to influenza vaccination in haematopoietic stem cell transplant recipients following reconstitution of humoral and adaptive immunity","authors":"Wuji Zhang,&nbsp;Louise C Rowntree,&nbsp;Ramona Muttucumaru,&nbsp;Timon Damelang,&nbsp;Malet Aban,&nbsp;Aeron C Hurt,&nbsp;Maria Auladell,&nbsp;Robyn Esterbauer,&nbsp;Bruce Wines,&nbsp;Mark Hogarth,&nbsp;Stephen J Turner,&nbsp;Adam K Wheatley,&nbsp;Stephen J Kent,&nbsp;Sushrut Patil,&nbsp;Sharon Avery,&nbsp;Orla Morrissey,&nbsp;Amy W Chung,&nbsp;Marios Koutsakos,&nbsp;Thi HO Nguyen,&nbsp;Allen C Cheng,&nbsp;Tom C Kotsimbos,&nbsp;Katherine Kedzierska","doi":"10.1002/cti2.1456","DOIUrl":"https://doi.org/10.1002/cti2.1456","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Influenza causes significant morbidity and mortality, especially in high-risk populations. Although current vaccination regimens are the best method to combat annual influenza disease, vaccine efficacy can be low in high-risk groups, such as haematopoietic stem cell transplant (HSCT) recipients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We comprehensively assessed humoral immunity, antibody landscapes, systems serology and influenza-specific B-cell responses, together with their phenotypes and isotypes, to the inactivated influenza vaccine (IIV) in HSCT recipients in comparison to healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Inactivated influenza vaccine significantly increased haemagglutination inhibition (HAI) titres in HSCT recipients, similar to healthy controls. Systems serology revealed increased IgG1 and IgG3 antibody levels towards the haemagglutinin (HA) head, but not to neuraminidase, nucleoprotein or HA stem. IIV also increased frequencies of total, IgG class-switched and CD21^loCD27⁺ influenza-specific B cells, determined by HA probes and flow cytometry. Strikingly, 40% of HSCT recipients had markedly higher antibody responses towards A/H3N2 vaccine strain than healthy controls and showed cross-reactivity to antigenically drifted A/H3N2 strains by antibody landscape analysis. These superior humoral responses were associated with a greater time interval after HSCT, while multivariant analyses revealed the importance of pre-existing immune memory. Conversely, in HSCT recipients who did not respond to the first dose, the second IIV dose did not greatly improve their humoral response, although 50% of second-dose patients reached a seroprotective HAI titre for at least one of vaccine strains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrates efficient, although time-dependent, immune responses to IIV in HSCT recipients, and provides insights into influenza vaccination strategies targeted to immunocompromised high-risk groups.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"12 6","pages":""},"PeriodicalIF":5.8,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5880939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}