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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Richard Palmqvist, Umeå University, Sweden
- Second opponent: Associate Professor Lars Helgeland, University of Bergen
- Third member and chair of the evaluation committee: Professor Marit Inngjerdingen, University of Oslo
Chair of the Defence
Professor Farrukh Abbas Chaudry, University of Oslo
Principal Supervisor
Associate Professor Sheraz Yaqub, University of Oslo
Summary
Colorectal cancer (CRC) is the third most frequent cancer globally with almost 2 million new cases each year and is a major health problem. Macrophages, a type of immune cell, play a crucial role in both healthy tissue and cancer development. However, the heterogeneity of macrophages in CRC and their impact on prognosis is not fully understood. This study aimed to characterize the heterogeneity of macrophages in the healthy large intestine and CRC in humans.
First we investigated the macrophages in healthy colon, and using single-cell RNA sequencing (scRNA-Seq) found that the different anatomical layers had different subsets of macrophages. In the mucosa we found that monocyte derived macrophages matured towards the luminal part of the epithelium, and could develop into several different transcriptional states, like proinflammatory, immunoregulatory, and antigen-presenting subsets. In muscularis the macrophages were involved in neural homeostasis, immune activation and angiogenesis.
Next, we evaluated the prognostic effect of tumoral macrophages in CRC using tissue microarray (TMA) with samples from 1.720 patients. We found that higher macrophage density is associated with better relapse free survival. However, this effect was dependent on T cell density of the tumor.
Using single-cell RNA sequencing to examine the heterogeneity among tumoral macrophages and multiplex immunofluorescence stainings to analyze TMA we found that patients with higher infiltration of GBP1+ and FOLR2+ macrophages have increased 5-year overall and relapse free survival. These findings were for microsatellite stable tumors.
In summary, the work in this study has demonstrated the diversity and heterogeneity among macrophages in the healthy colon and colorectal cancer, and shows that macrophages in collaboration with T cells influence the survival of colorectal cancer patients.
Additional information
Contact the research support staff.