Immunoprofiling in Lynch syndrome urinary tract cancers

Maria Rasmussen1, Mats Jönsson2, Eva Rambech2, Ove Andersen1, Mef Nilbert1,2,3, Christina Therkildsen1

1The Danish HNPCC Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Hvidovre, Denmark. 2Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. 3The Danish Cancer Society Research Center, Copenhagen, Denmark

Abstract

Objectives

Immune therapy is used as a treatment of cancers with a high mutational load, which includes urinary tract cancers. Recently, PD-L1 has been shown to be a predictive marker for treatment response in these cancers. Studies on immune response and immune evasion mechanisms for urinary tract tumors are scarce and it remains unknown how Lynch syndrome urinary tract tumours evade the immune system.

Methods

Immunohistochemical and gene expression data is planned on a national Lynch syndrome cohort of urinary tract tumours. Tumours are collected from pathology departments all around Denmark and stained using antibodies against a variety of immune cell types which are CD3 (T cells), CD8 (cytotoxic T cells), CD68 (pro-inflammatory macrophages), CD20 (B cells), FOXP3 (regulatory T cells), CD56 and CD244 (natural killer cells), and different immune evasion regulators such as B2M, CTLA-4, B7.1, B7.2, PD1, PD-L1, TIM-3, Galectin 9, and LAG-3.

Results

In total, 186 urinary tract tumors were identified among 134 carriers of pathogenic mismatch repair gene mutations from 97 Lynch syndrome families. Among the tumours, 51 tumours developed in renal pelvis, 60 in the ureter, and 75 in the bladder. The immunohistochemical staining will be performed during summer 2019 and the results will be presented on the poster.

Conclusions

The results are expected to describe the different immune evasion mechanisms used in Lynch syndrome-associated urinary tract cancers. These results may impact future immunological therapy since the rationale for these treatments may be influenced by the expression of target-receptors.

 

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