PD-1-positive cells contribute to the diagnosis of inflammatory bowel disease and can aid in predicting response to vedolizumab

Kim, Min Kyu; Jo, Su In; Kim, Sang-Yeob; Lim, Hyun; Kang, Ho Suk; Moon, Sung‑Hoon; Ye, Byong Duk; Soh, Jae Seung; Hwang, Sung Wook

doi:10.1038/s41598-023-48651-y

Cited by 3 publications

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A pilot study to identify blood-based markers associated with response to treatment with Vedolizumab in patients with Inflammatory Bowel Disease

Rioux,

Boucher,

Forest

et al. 2024

Preprint

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The inflammatory bowel diseases (IBD) known as Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract believed to arise because of an imbalance between the epithelial, immune and microbial systems. It has been shown that biological differences (genetic, epigenetic, microbial, environmental, etc.) exist between patients with IBD, with multiple risk factors been associated with disease susceptibility and IBD-related phenotypes (e.g. disease location). It is also known that there is heterogeneity in terms of response to therapy in patients with IBD, including to biological therapies that target very specific biological pathways (e.g. TNF-alpha signaling, IL-23R signaling, immune cell trafficking, etc.). It is hypothesized that the better the match between the biology targeted by these advanced therapies and the predominant disease-associated pathways at play in each patient will favor a beneficial response. The aim of this pilot study was to identify potential biological differences associated with differential treatment response to the anti α4β7 integrin therapy known as Vedolizumab. Our approach was to measure a broad range of analytes in the serum of patients prior to initiation of therapy and at the first clinical assessment visit, to identify potential markers of biological differences between patients at baseline and to see which biomarkers are most affected by treatment in responders. Our focus on early clinical response was to study the most proximal effects of therapy and to minimize confounders such as loss of response that occurs further distal to treatment initiation. Specifically, we performed targeted analyses of >150 proteins and metabolites, and untargeted analyses of >1100 lipid entities, in serum samples from 92 IBD patients (42 CD, 50 UC) immediately prior to initiation of therapy with vedolizumab (baseline samples) and at their first clinical assessment (14-week samples). We found lower levels of SDF-1a, but higher levels of PDGF-ββ, lactate, lysine, phenylalanine, branched chain amino acids, alanine, short/medium chain acylcarnitines, and triglycerides containing myristic acid in baseline serum samples of responders as compared to non-responders. We also observed an increase in serum levels of CXCL9 and citrate, as well as a decrease in IL-10, between baseline and week 14 samples. In addition, we observed that a group of metabolites and protein analytes was strongly associated with both treatment response and BMI status, although BMI status was not associated with treatment response.

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A pilot study to identify blood-based markers associated with response to treatment with Vedolizumab in patients with Inflammatory Bowel Disease

Rioux,

Boucher,

Forest

et al. 2024

Preprint

View full text Add to dashboard Cite

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Cellular immunotherapies and immune cell depleting therapies in inflammatory bowel diseases: the next magic bullet?

Neurath,

Sands,

Rieder

2024

Gut

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Despite significant advances in biologic and small molecule treatments and the emergence of combination therapies to treat inflammatory bowel diseases (IBD) a large unmet need remains to control intestinal inflammation. New approaches targeting several pathways simultaneously with a favorable safety profile and agents that trigger anti-inflammatory pathways to drive durable resolution of inflammation are needed. This article discusses novel cellular immunotherapies and immune cell depleting therapies in IBD, including CAR-T cell approaches, Tr1 and T regulatory (Treg) cells and cell depleting antibodies such as rosnilimab. These novel approaches have the potential to overcome current therapeutic limitations in the treatment of IBD.

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CD8+ cell dominance in immune checkpoint inhibitor-induced colitis and its heterogeneity across endoscopic features

Kim,

Son,

Hong

et al. 2024

Therap Adv Gastroenterol

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Background: Immune checkpoint inhibitor (ICI)-induced colitis is a significant adverse event associated with ICI therapy, known to be linked to increased cytotoxic T-cell activity. Objectives: To compare T-cell subsets based on the endoscopic features of ICI-induced colitis and to compare these findings with those of inflammatory bowel disease (IBD). Design: Prospective cohort study. Methods: We analyzed patients with ICI-induced colitis, confirmed through both endoscopic and histological evaluation. Biopsy specimens were examined using multiplex immunohistochemistry to assess their immune cell profile. Clinical outcomes were analyzed. Immune cell profiles were compared based on their endoscopic features and contrasted with those of patients with IBD. Results: Seventeen patients with ICI-induced colitis were included in the study. All patients showed clinical improvement after treatment, and steroids were administered to 11 patients (64.7%). Based on endoscopic features, the patients were classified as Crohn’s disease (CD)-like ( n = 3, 17.6%), ulcerative colitis (UC)-like ( n = 9, 52.9%), or microscopic colitis (MC)-like ( n = 5, 29.4%). In ICI-induced colitis, cytotoxic T cells (Tc cells) were more predominant than helper T cells (Th cells) ( p = 0.053), and this trend was most pronounced in the MC-like subtype ( p = 0.020). When comparing the number of CD8+ cells infiltrating the crypts, both the UC-like and MC-like subtypes had significantly more infiltrating cells than the CD-like subtype ( p = 0.008 and p = 0.016, respectively). In comparison to IBD, IBD exhibited a Th-dominant profile, whereas CD-like ICI-induced colitis had a lower Th cell density than CD ( p = 0.032) and UC-like ICI-induced colitis had a higher Tc density than UC ( p = 0.045). Conclusion: Analysis of T-cell subsets of ICI-induced colitis revealed a Tc-dominant profile, contrasting with the Th dominance observed in patients with IBD. The Tc-dominant profile was evident in UC-like and MC-like subtypes, with significant crypt infiltration by CD8+ cells. Tc may play an important role in the pathophysiology of ICI-induced colitis.

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PD-1-positive cells contribute to the diagnosis of inflammatory bowel disease and can aid in predicting response to vedolizumab

Cited by 3 publications

References 50 publications

A pilot study to identify blood-based markers associated with response to treatment with Vedolizumab in patients with Inflammatory Bowel Disease

A pilot study to identify blood-based markers associated with response to treatment with Vedolizumab in patients with Inflammatory Bowel Disease

Cellular immunotherapies and immune cell depleting therapies in inflammatory bowel diseases: the next magic bullet?

CD8+ cell dominance in immune checkpoint inhibitor-induced colitis and its heterogeneity across endoscopic features

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