title: Intraoperative intravital microscopy permits the study of human tumour vessels.
abstract: Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment.
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Fisher
authors.affiliation: Department of Urology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Muhitch
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.|Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Minhyung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Spectra Services, Incorporated, Ontario, New York 14519, USA.
authors.forename: Kurt C
authors.initials: KC
authors.lastname: Doyen
authors.affiliation: Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Bogner
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Sharon S
authors.initials: SS
authors.lastname: Evans
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.|Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Skitzki
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000737:chemistry*; D045744:Cell Line, Tumor; D006801:Humans; D000069416:Intravital Microscopy / Q000379:methods*; D008545:Melanoma / Q000098:blood supply / Q000737:chemistry* / Q000503:physiopathology; D051379:Mice; D008833:Microcirculation