title: Tumor-infiltrating lymphocyte subsets and tertiary lymphoid structures in pulmonary metastases from colorectal cancer.
abstract: The presence of tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) reflects an active inflammatory tumor microenvironment. High density of TILs as well as presence of TLS is associated with improved survival in various solid cancer types. We aimed to describe the density and distribution of TILs and TLS in pulmonary metastases (PMs) from primary colorectal cancer (CRC) and its correlation with clinicopathological variables. Fifty-seven CRC pulmonary metastasectomy specimen (PM) and 31 matched primary CRC specimen were included. Cluster of differentiation (CD)3+, CD8+, CD45RO+ and FoxP3+ TILs were evaluated by immunohistochemistry and density was scored semiquantitatively. TLS were evaluated based on morphological criteria. Survival time was defined from pulmonary metastasectomy to death or last follow up. A marked infiltration with CD3+, CD8+, CD45RO+ and FoxP3+ TILs was evident in CRC PM and matched primary CRC. Further assessment of the immune infiltrate in PM showed that a high density of FOXP3+ TILs at the invasive margin [HR 2.40 (1.11-6.96); P = 0.031] and low density of CD8+ cells in TLS [HR 0.30 (0.14-0.79); P = 0.016] were associated with a worse prognosis in univariate analysis. Moreover, a low CD8/FoxP3-ratio of TILs at the invasive margin (P = 0.042) and in TLS (P = 0.027) conferred an impaired prognosis after pulmonary metastasectomy. Our findings suggest that CRC PM harbor an immune active microenvironment. The balance of CD8+ and FoxP3+ T-cells at the tumor border and in TLS provides prognostic information in patients with CRC PM.
authors.affiliation: Division of Thoracic Surgery, Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schweiger
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Anna Sophie
authors.initials: AS
authors.lastname: Berghoff
authors.affiliation: Division of Thoracic Surgery, Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Glogner
authors.affiliation: Division of Thoracic Surgery, Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
authors.forename: Olaf
authors.initials: O
authors.lastname: Glueck
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Rajky
authors.affiliation: Division of Thoracic Surgery, Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Vienna, Austria.
authors.forename: Denise
authors.initials: D
authors.lastname: Traxler
authors.affiliation: Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.affiliation: Division of Thoracic Surgery, Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.affiliation: Division of Thoracic Surgery, Department of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. konrad.hoetzenecker@meduniwien.ac.at.
authors.forename: Konrad
authors.initials: K
authors.lastname: Hoetzenecker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000556:secondary; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D000072717:Tertiary Lymphoid Structures / Q000276:immunology / Q000473:pathology; D059016:Tumor Microenvironment / Q000276:immunology
keywords: Colorectal cancer; Pulmonary metastasis; TILs; Tertiary lymphoid structures; Tumor-infiltrating lymphocytes