title: Analysis of the intratumoral adaptive immune response in well differentiated and dedifferentiated retroperitoneal liposarcoma.
abstract: Treatment options are limited in well differentiated (WD) and dedifferentiated (DD) retroperitoneal liposarcoma. We sought to study the intratumoral adaptive immune response and explore the potential feasibility of immunotherapy in this disease. Tumor-infiltrating lymphocytes (TILs) were isolated from fresh surgical specimens and analyzed by flow cytometry for surface marker expression. Previously reported immune cell aggregates known as tertiary lymphoid structures (TLS) were further characterized by immunohistochemistry. In all fresh tumors, TILs were found. The majority of TILs were CD4 T cells; however cytotoxic CD8 T cells were also seen (average: 20% of CD3 T cells). Among CD8 T cells, 65% expressed the immune checkpoint molecule PD-1. Intratumoral TLS may be sites of antigen presentation as DC-LAMP positive, mature dendritic cells were found juxtaposed next to CD4 T cells. Clinicopathologic correlation, however, demonstrated that presence of TLS was associated with worse recurrence-free survival in WD disease and worse overall survival in DD disease. Our data suggest that an adaptive immune response is present in WD/DD retroperitoneal liposarcoma but may be hindered by TLS, among other possible microenvironmental factors; further investigation is needed. Immunotherapy, including immune checkpoint blockade, should be evaluated as a treatment option in this disease.
authors.affiliation: Department of Surgery, Section of Surgical Oncology, University of Southern California, Los Angeles, CA 90033, USA ; Hoag Memorial Hospital Presbyterian, Newport Beach, CA 92663, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Tseng
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Malu
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Minying
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jieqing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Geok Choo
authors.initials: GC
authors.lastname: Sim
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Davis
authors.identifier: 0000-0001-5967-1501
authors.initials: D
authors.lastname: Ingram
authors.affiliation: Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Neeta
authors.initials: N
authors.lastname: Somaiah
authors.affiliation: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Dina C
authors.initials: DC
authors.lastname: Lev
authors.affiliation: Division of Surgical Oncology, The James Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Raphael E
authors.initials: RE
authors.lastname: Pollock
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Lizée
authors.affiliation: Lion Biotechnologies, Woodland Hills, CA 91637, USA ; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Radvanyi
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA ; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hwu