O094 Urinary-derived immune cell profiling to predict bladder cancer progression and treatment response

Abstract

Abstract Introduction A quarter of newly diagnosed bladder cancers are muscle-invasive (MIBC) (45% 5-year disease free survival). 30% patients with apparent non-muscle-invasive cancer (NMIBC) have MIBC on histology following cystectomy (RARC). Tumour associated macrophages (TAMs) polarise into an immunogenic M1 phenotype or immunosuppressive M2 phenotype. This study assesses accuracy and validity of quantifying urinary macrophages for earlier recognition of treatment resistant bladder cancer. Methods Urine-derived cells and tumour and adjacent normal bladder derived cells were collected from 18 RARC patients between May-October 2022. Flow cytometry performed for immune cell profiling (MACSQuant). Results The urinary immune cell profile closely reflected the tumour immune profile. Females had higher CD206+CD163+ M2 phenotype cells in urine and in tumour (p<0.05). In adjacent normal bladder and in males we identified higher CD3+CD8+ T cell expression in tumour tissue (p<0.05) despite non-significant difference in distribution of male and female disease stage at final histology. NMIBC demonstrated an immunogenic urinary and tumour profile with more M1 macrophages (CD68+CD80+) (p<0.05) vs. MIBC. The 3 males upstaged from NMIBC to MIBC on final histology had lower representation of CD68+CD80+ M1 phenotype cells in urine and tumour (p<0.05). Conclusion The TAM immune cell profile is reflected accurately in urine sampled at RARC: a higher proportion of M2 phenotypic macrophages and lower proportion of M1 macrophages in the tumour and urine is predictive of more aggressive disease. This study highlights the potential application of urinary derived TAM analysis for disease outcome prediction and early consideration of adjuvant immune checkpoint therapy.