Patient characteristics
The clinical characteristic of Cohort 1, from which gut-derived mononuclear cells were studied, are shown in Table Ia). There were no significant differences between IN-COL and IN-NAE groups in regard to age, sex, melanoma stage, presence of visceral metastasis or serum LDH. Cohort 1 IN-C patients were managed with IVMP (33%), mycophenolate mofetil 500-1000mg twice daily (17%), infliximab 5mg/kg (33%) or vedolizumab 300mg Weeks 0, 2 and 6 (17%). The clinical characteristics of patients with UC in Cohort 1 are shown in Table Ib). These patients had a median disease duration of 4 years and had been treated with mesalazine (3/6), azathioprine (1/6), infliximab (1/6) and adalimumab (1/6). The clinical, endoscopic and histopathological features of Cohort 1 UC and IN-COL are shown in Table Ic). While there was no difference in sex, UC patients were significantly younger (36 versus 66 years) and had a longer duration since the initial colitis diagnosis (48 versus 1 month). There were no significant differences in disease severity score using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) on Nancy histological score (Table Ic).
Clinical characteristics of patients in Cohort 2, from which PBMC were studied, are shown in Table IIa). All Cohort 2 patients with colitis had high-grade disease confirmed by flexible sigmoidoscopy or colonoscopy and histopathology. The range of histopathological findings are given in Table IIa). There was no significant difference between melanoma patient groups in terms of age, sex, melanoma stage or serum lactate dehydrogenase (LDH) level. The IN-COL “colitis” sample timepoint did not differ significantly in terms of time (days) from the IN-NAE week 7-10 “TX sample” time-point. Intravenous methylprednisone (IVMP) 1mg/kg for 1-3 days was used to manage IN-COL in 78% of patients and infliximab (IFX) 5mg/kg given once was used in 78% of IN-COL patients. The tumour response to ICIs was comparable between groups (IN-COL: Progressive Disease=4, Stable Disease=0; Partial Response=1; Complete Response=4 and IN-NAE: Progressive Disease=3; Stable Disease=0; Partial Response=3; Complete Response=5). The clinical characteristics of patients with UC in Cohort 2 are shown in Table IIb). These patients had a disease duration of 5 years and had been treated with mesalazine (5/6), azathioprine (5/6), prednisone (4/6) and/or infliximab (3/6). All patients with UC were in a state of disease flare at the time of blood sampling as determined by clinical features and/or endoscopy and histopathology.
The clinical characteristics of patients in Cohort 3 are shown in Table III. Patients in the IN-COL and IN-NAE group had no significant difference in age, sex, melanoma stage, proportion with visceral metastasis or serum LDH. There were no differences in IN-COL group patient factors between Cohort 2 and Cohort 3. In regard to the IN-NAE patients, Cohort 3 had earlier stage disease compared with Cohort 2 (p<0.05).