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Supplementary Figures and Tables

Table S4

For anthracycline-based chemotherapy to be immunogenic, dying cancer cells must release annexin A1 (ANXA1) that subsequently interacts with the pattern recognition receptor, formyl peptide receptor 1 (FPR1), on the surface of dendritic cells (DC). Approximately 30% of individuals bear loss-of-function alleles of FPR1, calling for strategies to ameliorate their anticancer immune response. Here, we show that immunotherapy with a ligand of Toll-like receptor-3, polyinosinic:polycytidylic acid (pIC), restores the deficient response to chemotherapy of tumors lacking ANXA1 developing in immunocompetent mice or those of normal cancers growing in FPR1-deficient mice. This effect was accompanied by improved DC- and T-lymphocyte–mediated anticancer immunity. Of note, carcinogen-induced breast cancers precociously developed in FPR1-deficient mice as compared with wild-type controls. A similar tendency for earlier cancer development was found in patients carrying the loss-of-function allele of FPR1. These findings have potential implications for the clinical management of FPR1-deficient patients.Significance:The loss-of-function variant rs867228 in FPR1, harbored by approximately 30% of the world population, is associated with the precocious manifestation of breast, colorectal, esophageal, and head and neck carcinomas. pIC restores deficient chemotherapeutic responses in mice lacking Fpr1, suggesting a personalized strategy for compensating for the FPR1 defect.This article is highlighted in the In This Issue feature, p. 211

International audience; PURPOSE OF REVIEW: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.RECENT FINDINGS: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.SUMMARY: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.