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• W4295828361 abstract "Pancreatic Ductal Adenocarcinoma (PDAC) is considered a cold tumour and immune checkpoint inhibitors have proved unsuccessful thus far. Despite this there is variability in the number of intratumoral CD8+ T cells across the malignant epithelium and the microenvironment (TME). We evaluated CD8 staining in FFPE sections in an unselected subset of patients enrolled on the COMPASS trial. Immunohistochemical staining was performed using the antibody CD8-4B11-L-CE. Tumoural regions were reviewed and annotated by a pathologist and digital image analysis (QuPath) enumerated the number of positive cells per mm2. Samples were classified as CD8hi vs CD8lo using the median no./mm2. Fisher’s exact test, student’s t-test and Mann Whitney test were used to explore associations; Kaplan Meier analyses evaluated impact on OS. Clinical and molecular data were integrated into analyses and included HRDetect scores, the modified Moffitt classifier (basal-like and classical) and the Gustave Roussy immune score (GRIm-S). Of the 268 patients enrolled on the COMPASS trial, 136 patients have had baseline tumours stained for CD8. Of these, a sample from the primary tumour was used in 35% (n=47) and a metastatic site in 65% (n=89). The median number of CD8+ cells was 137/mm2. More primary samples were CD8hi compared to mets (69% vs 46%; p=0.02) with a median CD8 count of 171/mm2 in primaries compared to 104/mm2 in metastatic sites. There was no difference in CD8+ T cell infiltrate according to sex (p=0.46), BMI (p=0.9), age (p=0.86) or smoking status (p=0.17). In addition there was no association with the HRDetect score (p=0.78) or basal-like/classical subgroups (p=0.9). Those patients with high GRIm-S tended to have low CD8 infiltrates (p=0.03). In a univariable analysis the CD8hi group had improved OS vs CD8lo (median OS 11.0 vs 6.44 mths, HR 0.70, 95% CI 0.49-0.99; p=0.04). Higher CD8+ T cell infiltration associated with improved OS in advanced PDAC patients across transcriptomic subtypes and a variety of epidemiologic variables. Primary tumours may have higher numbers of CD8+ T cells compared to metastatic sites. The lack of association of CD8 with RNA based classifiers suggests heterogeneity in the TME within these subgroups." @default.
• W4295828361 created "2022-09-15" @default.
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• W4295828361 date "2022-09-01" @default.
• W4295828361 modified "2023-10-11" @default.
• W4295828361 title "1309P CD8+ T cell infiltration is associated with improved survival in advanced pancreatic cancer" @default.
• W4295828361 doi "https://doi.org/10.1016/j.annonc.2022.07.1441" @default.
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