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Cancer immunotherapy has primarily been focused on attacking tumor cells. However, given the close interaction between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), CAF-targeted strategies could also contribute to an integrated cancer immunotherapy. Fibroblast activation protein α (FAP α) is not detectible in normal tissues, but is overexpressed by CAFs and is the predominant component of the stroma in most types of cancer. FAP α has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. When all FAP α-expressing cells (stromal and cancerous) are destroyed, tumors rapidly die. Furthermore, a FAP α antibody, FAP α vaccine, and modified vaccine all inhibit tumor growth and prolong survival in mouse models, suggesting FAP α is an adaptive tumor-associated antigen. This review highlights the role of FAP α in tumor development, explores the relationship between FAP α and immune suppression in the TME, and discusses FAP α as a potential immunotherapeutic target., Competing Interests: No potential conflicts of interest were disclosed.

Fibroblast activation protein α (FAPα) is a potential target for cancer therapy. However, elimination of FAPα+ fibroblasts activates secretion of IFN-γ and TNF-α. IFN-γ can in turn induce expression indolamine-2,3-dioxygenase (IDO), thereby contributing to immunosuppression, while TNF-α can induce EMT. These two reactive effects would limit the efficacy of a tumor vaccine. We found that curcumin can inhibit IDO expression and TNF-α-induced EMT. Moreover, FAPαc vaccine and CpG combined with curcumin lavage inhibited tumor growth and prolonged the survival of mice implanted with melanoma cells. The combination of FAPαc vaccine, CpG and curcumin stimulated FAPα antibody production and CD8+ T cell-mediated killing of FAPα-expressing stromal cells without adverse reactive effects. We suggest a combination of curcumin and FAPαc vaccine for melanoma therapy.

Objective: To detect the mRNA and protein expression of interferon-inducible transmembrane protein-1 (IFITM1) in Peutz-Jeghers syndrome (PJS) and investigate the role of IFITM1 in the occurrence, development and carcinogenesis of PJS polyps., Methods: Reverse transcription-PCR was employed to detect the mRNA expression of IFITM1 in 16 PJS polyp samples, adenomatous polyp tissues, colon adenocarcinoma samples, and normal intestinal mucosal tissues. The protein expression and localization of IFITM1 in these tissues (32 cases for each) were detected with immunohistochemical (IHC) staining., Results: The IFITM1 mRNA expression was detected in all these tissues, and the expression intensity increased in the order of normal intestinal mucosa, PJS polyp, adenomatous polyp, and colon adenocarcinoma (F=92.704, P=0.000). IHC revealed that IFITM1 protein was localized mainly on the cell membrane and in the cytoplasm, with increased expression intensity in the same order as its mRNA and showing significant differences between the tissues by several rank-sum test (Kruskal-Wallis H, chi(2)=37.036, p=0.000)., Conclusion: The expression level of IFITM1 is associated with the progression of the carcinogenetic process in PJS polyp, and can be used as a sensitive biomarker for diagnosis and prognostic evaluation of PJS.