This thesis describes six studies which characterized tumor-infiltrating leukocytes (TIL) in colorectal cancer. TIL have shown to be of importance in the natural anti-tumor immunity of cancer... Show moreThis thesis describes six studies which characterized tumor-infiltrating leukocytes (TIL) in colorectal cancer. TIL have shown to be of importance in the natural anti-tumor immunity of cancer patients. Chapter 1 gives an introductory overview of tumor immunology, TIL and colorectal cancer. In chapter 2 we describe the presence, location, and phenotype of tumor-infiltrating dendritic cells in colorectal cancer. With special attention to their association with other tumor-infiltrating immune cells, i.e. lymphocytes. Chapter 3 elaborates further on the role of tumor-infiltrating DC by evaluating whether there is an association between the presence and maturation status of tumor-infiltrating DC, T lymphocytes and clinical prognosis in patients with colorectal cancer. In chapter 4 NK cell infiltration in colorectal cancer is studied in relationship with loss of tumor MHC class I expression. In chapter 5 TIL were characterized in a case-control design, with tumors showing complete absence or normal expression of HLA class I. We further characterized TIL in a group of colorectal tumors displaying systemic P53 reactivity in chapter 6. Chapter 7 describes the technique of the multi-color immunohistochemical analysis, which we used to characterize the phenotype of TIL in the two preceding chapters. Chapter 8 Summary and Discussion. Show less
Diffuse large B cell lymphoma is the most common type of non-Hodgkin lymphoma of which 40% present at extra-nodal sites including immune privileged sites such as the testis and the central nervous... Show moreDiffuse large B cell lymphoma is the most common type of non-Hodgkin lymphoma of which 40% present at extra-nodal sites including immune privileged sites such as the testis and the central nervous system (CNS). Loss of Human Leucocyte Antigen (HLA) expression has been described in many different tumour types as a mechanism to evade anti-tumour immune responsen. In testicular and CNS lymphomas HLA class I and II expression was very commonly observed in contrast to nodal, stomach and skin lymphomas that expressed HLA in most of the cases. Loss of HLA-DR and DQ expression was often due to homozygous deletions of the corresponding genes. Loss of class I expression was often caused by loss of Beta-2-microglobulin expression and hemizygous deletions. Despite their immune privileged status, the testicular and CNS lymphomas showed high numbers of activated cytotoxic T cells, suggesting that these lymphomas are highly immunogenic. DNA-typing for HLA-DR and DQ polymorphisms in testicular and nodal lymphomas revealed a positive association of testicular lymphomas with HLA-DRB1*12 and a negative association of nodal lymphomas with HLA-DRB1*07. Both testicular and nodal lymphomas showed a positive association with HLA-DRB1*15. No significant relationship was found between the different haplotypes and the occurrence of homozygous deletions in the testicular lymphomas. Show less
