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.
Resources from the same session
3489 - Overall Survival (OS) and Metastasis-Free Survival (MFS) in men with Biochemically Relapsed (BCR) Prostate Cancer after radical prostatectomy (RP) managed with deferred Androgen Deprivation Treatment (ADT): A combined Johns Hopkins and CPDR study
Presenter: Catherine Marshall
Session: Poster Display session 3
Resources:
Abstract
4606 - ARCHES – the role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of high and low disease volume and risk groups
Presenter: Arnulf Stenzl
Session: Poster Display session 3
Resources:
Abstract
2975 - Updated survival analyses of a multicentric phase II randomized trial of docetaxel (D) plus enzalutamide (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (CHEIRON study).
Presenter: Orazio Caffo
Session: Poster Display session 3
Resources:
Abstract
2708 - Real-world analysis of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving vs not receiving chemotherapy in the treatment sequence
Presenter: Alicia Morgans
Session: Poster Display session 3
Resources:
Abstract
2134 - Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial
Presenter: Janet Brown
Session: Poster Display session 3
Resources:
Abstract
3504 - Risk of falls and fractures in patients with castration resistant prostate cancer (CRPC) treated with new hormonal agents – a meta-analysis of randomized controlled trials.
Presenter: Rodrigo Coutinho Mariano
Session: Poster Display session 3
Resources:
Abstract
2342 - Pain progression at initiation of chemotherapy in metastatic Castration-Resistant Prostate Cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of FIRSTANA
Presenter: Nicolas Delanoy
Session: Poster Display session 3
Resources:
Abstract
5331 - Pain evaluation in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the PARABO observation study
Presenter: Holger Palmedo
Session: Poster Display session 3
Resources:
Abstract
2823 - Time to castration resistant prostate cancer (CRPC) and the risk of developing immune disorders
Presenter: Vincenza Conteduca
Session: Poster Display session 3
Resources:
Abstract
1500 - Retrospective evaluation of neutropenic admission events in metastatic or high-risk hormone-sensitive prostate cancer (HSPC) patients having docetaxel chemotherapy upfront or for castrate-resistant prostate cancer (CRPC) in STAMPEDE
Presenter: Harriet Mintz
Session: Poster Display session 3
Resources:
Abstract