Immune contexture of cholangiocarcinoma

Considering the failure of standard treatments (i.e. surgery, radiotherapy, chemotherapy) in treating cholangiocarcinoma (CCA), introduction of alternative interventions is urgently needed. During the past 2 decades, discoveries of the mechanisms of cancer immunosurveillance and tumor immune evasion have precipitated the emergence and clinical approval of immunotherapies in multiple malignant indications. Interest in their introduction for the care of CCA is recent and several immunotherapeutic approaches are undergoing a clinical evaluation. Undoubtedly, their efficient application, as monotherapy or in combination regimens, will rely on a deeper understanding of CCA immune contexture.

CCA cells appeared very potent in recruiting protumorigenic cells and shaping an immunosuppressive microenvironment. Elevated densities of several immune cells with immunoinhibitory activities within the malignant bed have been associated with poor prognosis in patients. Particularly, macrophages and neutrophils (especially in their alternatively activated phenotype) were pointed out for their role in cancer progression. Dendritic cells were described as ineffective in priming CCA-specific T-cell responses.

Quantitative and qualitative assessment of the innate and adaptive immune compartments of the CCA immune contexture, as well as their prognostic value, will benefit to the development of improved immunotherapeutic strategies.