Colorectal cancer accounts for ten percent of new cancer cases and is the fourth most frequent cause of cancer-related deaths worldwide. In recent years, mainly due to screening programs, more patients are diagnosed in early stages of tumor progression, leading to a higher survival rate. However, the incidence of young (<50) patients diagnosed with colorectal cancer has been on the rise. These patients often have a poor prognosis due to the fact that tumors are diagnosed at advanced stages of tumor progression.

To our knowledge, no study has yet characterized immunophenotypes and immune evasive mechanisms specifically in young-onset colorectal cancers. To that end we have investigated the expression of HLA class I and PD-L1 in over 200 colorectal cancers derived from young-onset (< 50 years-old) patients. Furthermore, we applied a novel multispectral immunofluorescence technology to perform multiparameter immunophenotyping with CD3, CD8, PD-1, PD-L1, CD163, and Ki-67 in the same cohort.

We describe that HLA class I expression is maintained in the large majority of tumors allowing thus the development of neo-antigen targeted therapies. Interestingly, reduced expression of HLA class I but not total loss was associated with liver metastases, which suggests a specific selective pressure at this organ that might warrant tailored immune therapeutic interventions. As previous studies on colorectal cancer demonstrated, PD-L1 expression is limited and often restricted to immune cell compartments. The presence of immune cell infiltrates was related to the mutation background of tumors but also to their HLA class I phenotype: tumors with altered HLA class I expression were more likely to present traces of lymphocyte-mediated anti-tumor immunity.

Retained HLA class I expression in the majority of colorectal cancers associated with low infiltration by effector immune cells suggests the therapeutic induction of anti-tumor immune responses in young-onset colorectal cancers, for instance, by means of neo-antigen-targeted therapies. We are currently assessing the frequency of natural recognition of neo-antigens in an autologous setting in young-onset, late-stage colorectal cancers.

This work was supported by the Fight Colorectal Cancer-Michael’s Mission-AACR Fellowship in Young-Onset, Late-Stage Colorectal Cancer Research awarded to N.F.C.C. de Miranda (15-40-1645-DEMI)

Citation Format: M E. van Herk, M Lee, M Rytterdahl, M E. Kop, A F. Ramalheiro, R van der Breggen, T van Wezel, H Morreau, E S. Jordanova, N F. de Miranda. Immunophenotypes in young-onset colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2942. doi:10.1158/1538-7445.AM2017-2942