Fibroblast activation protein, a potential diagnostic and therapeutic target for cancer—reply

• Published in: Human pathology Vol. 45; no. 7; pp. 1553 - 1554
• Main Authors: Tchou, Julia, MD, PhD, Conejo-Garcia, Jose, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2014; Elsevier Limited
• Subjects: Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - metabolism; Female; Gelatinases - metabolism; Humans; Immunotherapy; Interferon; Lymphocytes; Membrane Proteins - metabolism; Pathology; Proteins; Serine Endopeptidases - metabolism; Studies
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2013.11.022

A second, perhaps more effective, strategy aims at targeting cells that express FAP by (1) conjugating toxins, cytokines, or radioisotope to FAP-specific antibodies as reviewed in Fischer et al [5]; as such, these toxins or radioisotope are expected to have a "bystander" deleterious effect on both FAP-expressing and non-FAP-expressing cells, that is, adjacent tumor cells; (2) eliminating FAP-expressing cells either using a genetic approach [6] or immunotherapy approach using chimeric antigen receptor T cells (CAR T cell) directed against FAP, which were designed to kill FAP-expressing cells [7]. Rather, we demonstrated that FAP expression in human breast cancer was observed not only in tumor-associated fibroblasts but also in other nonfibroblast stromal cells that expressed CD45 (a panleukocyte marker), CD14, CD11b, and HLA-DR, markers of TAMs. Because TAMs are known to have immunosuppressive functions within the tumor microenvironment, our results offer an alternate (or at least complementary) explanation to the results reported by Kraman et al [6].