Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 3

5650 - Tissue-based activation of mucosal-associated invariant T (MAIT) cells in combination ipilimumab and nivolumab checkpoint inhibitor (CI) colitis.

Date

30 Sep 2019

Session

Poster Display session 3

Presenters

Sarah Sasson

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

S.C. Sasson1, V.T.F. Cheung2, T. Gupta2, J.J. Zaunders3, K. Nahar4, C..M. Munier5, A. Olsson-Brown6, G. Ahlenstiel7, U. Palendira8, R.A. Scolyer9, M.S. Carlino10, G.V. Long11, A.M. Menzies12, A. Kelleher5, M. Payne13, B. Fairfax13, M.R. Middleton14, P. Klenerman1, O. Brain2

Author affiliations

  • 1 Translational Gastroenterology Unit, Nuffield Department Of Medicine, University of Oxford, OX1 3PA - Oxford/GB
  • 2 Department Of Gastroenterology, John Radcliffe Hospital, Oxford/GB
  • 3 Centre For Applied Medical Research, St Vincent's Hospital, Sydney/AU
  • 4 Medical Oncology, The Melanoma Institute Australia, Sydney/AU
  • 5 Ivpp, The Kirby Institute, Sydney/AU
  • 6 Department Of Medical Oncology, Liverpool Hospital, Liverpool/GB
  • 7 Department Of Gastroenterology, Blacktown Hospital, Sydney/AU
  • 8 Immunology, Centenary Institute, Sydney/AU
  • 9 Anatomical Pathology, Royal Prince Alfred Hospital, 2050 - Camperdown/AU
  • 10 Oncology, The Crown Princess Mary Cancer Centre, 2145 - Westmead/AU
  • 11 Oncology, Melanoma Institute Australia, 2065 - Wollstonecraft/AU
  • 12 Medical Oncology, Melanoma Institute Australia, University of Sydney, 2060 - North Sydney/AU
  • 13 Medical Oncology, The Churchill Hospital, Oxford/GB
  • 14 Medical Oncology, Churchill Hospital University of Oxford, OX3 7LE - Oxford/GB
More

Resources

Abstract 5650

Background

Up to 44% of patients receiving combination ipilimumab and nivolumab develop checkpoint-inhibitor-(CI) colitis, however its molecular pathogenesis is poorly understood. We aimed to characterise peripheral blood and gut mononuclear cells (PBMC; GMNC) in patients with CI-colitis and controls to gain insights into disease aetiology. We were particularly interested in activated, memory, gut-homing CD8+ T-cells and also the innate-like mucosal-associated invariant T (MAIT) cells that play important roles in mucosal immunity.

Methods

In Cohort I PBMC from patients with CI-colitis (N = 9) were compared with those from patients who received CI with no adverse-events (CI-controls; N = 11), patients with active ulcerative colitis (UC; N = 6) and Healthy Volunteers (N = 16). PBMC findings were tested in a second cohort (Cohort II; IN-Colitis N = 15; IN-NAE=9). GMNC were isolated in Cohort III (IN-colitis N = 5; IN-controls N = 5; UC N = 6; Healthy Volunteers N = 6). Flow-cytometric analysis was used throughout.

Results

CI-colitis patients had low circulating MAIT cells compared with CI-controls at baseline in Cohort I. Low levels of circulating MAIT cells in both CI-colitis and CI-controls (compared to Healthy Volunteers) were found in Cohort II. CI-treated patients had high levels of activated-memory T-cells in peripheral blood (CD8 + >CD4+) that included a gut-homing population, regardless of the development of colitis. However, activation of circulating MAIT cells was not evident. In gut tissue there was elevation of activated, granzyme-B+ MAIT cells in CI-colitis compared with CI-controls. CI-colitis was characterised by an activated-memory CD8+ lymphocytosis.

Conclusions

Melanoma patients can have low baseline circulating MAIT cells. In one cohort this associated with CI-colitis. In tissue, activated MAIT cells were elevated in CI-colitis. Further work is needed to determine which immune populations are useful for the prediction and prognostication of CI-colitis, and if MAIT cells contribute to tissue damage or repair.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Celgene.

Disclosure

S.C. Sasson: Research grant / Funding (institution): Celgene. V.T.F. Cheung: Speaker Bureau / Expert testimony: Janssen. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: Amgen; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck MSD; Advisory / Consultancy: Mass-Array; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche. M.R. Middleton: Advisory / Consultancy: Amgen; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Lilli; Advisory / Consultancy: Merck; Advisory / Consultancy: Millenium; Advisory / Consultancy: Novartis; Advisory / Consultancy: Physiomics; Advisory / Consultancy: Rignotec; Advisory / Consultancy: Roche. O. Brain: Speaker Bureau / Expert testimony: BMS; Research grant / Funding (institution): Celgene. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings