Citations 2
Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review
Cesano, Alessandra, Augustin, Ryan C. , Barrea, Luigi , Carturan, Alberto , Ho, Winson S. , Kather, Jakob Nikolas , Lu, Rongze O., McQuade, Jennifer L. , Najjar, Yana G. , Shen, Rhine R. , Warner, Allison Betof , Warren, Sarah H. , Ziv, Elad , Marincola, Francesco M, Augustin, Ryan, Carturan, Alberto , Najjar, Yana G , Ruella, Marco , Betof Warner, Allison , Warren, Sarah , Ziv, Elad , Bedognetti, Davide , Bruno, Tullia Carmela , Hammer, Christian , Kather, Jakob Nikolas , Kirchhoff, Tomas , Pietrobon, Violena , Ruella, Marco , Soldati, Laura , Spencer, Christine N. , Marincola, Francesco M.
Journal for ImmunoTherapy of Cancer | January 17, 2025 | Volume: 13 | Issue: 1 | Pages: e008876
Cancer immunotherapy—including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)—has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies. Recent advancements as well as novel approaches to address the limitations of current treatments are discussed here, with a specific focus on ICI and ACT.
The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome
Mohr, Sandra , Fritz, Nikola, Hammer, Christian , Martínez, Cristina , Berens, Sabrina , Schmitteckert, Stefanie , Wahl, Verena, Schmidt, Målin , Houghton, Lesley A. , Goebel‐Stengel, Miriam , Kabisch, Maria, Götze, Dorothea, Milovač, Irina , D’Amato, Mauro , Röth, Ralph , Mönnikes, Hubert, Engel, Felicitas , Gauss, Annika , Tesarz, Jonas , Raithel, Martin , Andresen, Viola , Frieling, Thomas , Pehl, Christian, Stein‐Thöringer, Christoph, Clarke, Gerard , Kennedy, Paul J. , Cryan, John F. , Spiller, Robert E. , Beltrán, Caroll J. , Madrid, Ana María , Torres, Verónica , Arce, Edith Pérez de , Herzog, Wolfgang , Sayuk, Gregory S. , Karamanolis, George, Pojskić, Lejla , Bustamante, Mariona , Rabionet, Raquel , Estivil, Xavier, Wouters, Mira M. , Rappold, Gudrun , Santos, Javier , Schaefert, Rainer , Niesler, Beate , Zheng, Tenghao , Engel, Felicitas , Gauss, Annika , Tesarz, Jonas , Raithel, Martin , Andresen, Viola , Frieling, Thomas , Keller, Jutta , Stein-Thöringer, Christoph , Clarke, Gerard , Kennedy, Paul J , Cryan, John F , Dinan, Timothy G , Quigley, Eamonn M M , Spiller, Robin , Madrid, Ana María , Pérez de Arce, Edith , Herzog, Wolfgang , Mayer, Emeran A , Sayuk, Gregory , Gazouli, Maria , Karamanolis, George , Kapur-Pojskič, Lejla , Bustamante, Mariona , Rabionet, Raquel , Estivil, Xavier , Franke, André , Lieb, Wolfgang , Boeckxstaens, Guy , Wouters, Mira M , Simrén, Magnus , Rappold, Gudrun A , Vicario, Maria , Santos, Javier , Schaefert, Rainer , Lorenzo-Bermejo, Justo , Niesler, Beate , D'Amato, Mauro , Houghton, L A , Martínez, Cristina , Zheng, Tenghao , Stein-Thöringer, Christoph K., Quigley, Eamonn M.M. , Torres, Verónica, Boeckxstaens, Guy E. , Simrén, Magnus , Bermejo, Justo Lorenzo
Journal of Cellular and Molecular Medicine | June 24, 2021 | Volume: 25 | Issue: 16 | Pages: 8047-8061
AbstractIrritable bowel syndrome (IBS) is a gut‐brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation‐predominant IBS (IBS‐C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta‐analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS‐C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow‐up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS‐C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.