title: NK cells and T cells cooperate during the clinical course of colorectal cancer.
abstract: Recent evidence suggests that natural killer (NK) cells are typically defective in infiltrating solid tumors, with the exception of gastrointestinal stromal tumors (GIST). Interestingly, however, infrequently infiltrating NK cells do not appear to have a direct effect on tumor progression. Here, prompted by the recent evidence that NK cell and T cell crosstalk may trigger, or enhance, tumor antigen-specific immune responses, we have tested the clinical significance of this reciprocal signaling. To this end, a tissue microarray constructed with 1410 colorectal carcinoma (CRC) patient specimens was stained with NK and T cell antigen-specific monoclonal antibodies, utilizing the immunoperoxidase staining technique. Cut-off scores for positive (>4 NK cells) and negative (≤4 NK cells) NK cell CRC patient samples were determined using receiver operating characteristic curve analysis. Using this approach, NK cells were detected in 423 (30%) of the 1410 CRC specimens evaluated. The number of NK cells was >4 in only 132 (9%) of CRC samples. Correlation of the immunohistochemical staining results together with analysis of the clinical course of the disease revealed that the infiltration of colorectal tumors with both NK cells and CD8+ T cells is associated with prolonged patient survival. In contrast, infiltration of tumors with NK cells in combination with CD3+and CD4+T lymphocytes had no detectable effect on the clinical course of the disease. These results suggest that NK cell and CD8+T cell crosstalk in the tumor microenvironment may benefit patient outcome and further, that the enumeration of infiltrating NK and CD8+T cells in CRC tumors may provide useful prognostic information.
authors.affiliation: Laboratory of Tumor Immunology and Immunotherapy; Institute of Translational Pharmacology; CNR , Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sconocchia
authors.affiliation: Institute of Pathology; University of Basel ; Basel, Switzerland.
authors.forename: Serenella
authors.initials: S
authors.lastname: Eppenberger
authors.affiliation: Institute of Surgical Research and Hospital Management; University of Basel ; Basel, Switzerland.
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli
authors.affiliation: Institute of Pathology; University of Basel ; Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
authors.affiliation: Institute of Surgical Research and Hospital Management; University of Basel ; Basel, Switzerland.
authors.forename: Raoul
authors.initials: R
authors.lastname: Droeser
authors.affiliation: Laboratory of Tumor Immunology and Immunotherapy; Institute of Translational Pharmacology; CNR , Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Caratelli
authors.affiliation: Institute of Systems Medicine; University of Rome "Tor Vergata" ; Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrelli
authors.affiliation: Institute of Systems Medicine; University of Rome "Tor Vergata" ; Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Coppola
authors.affiliation: Institute of Systems Medicine; University of Rome "Tor Vergata" ; Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Arriga
authors.affiliation: Institute of Systems Medicine; University of Rome "Tor Vergata" ; Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.affiliation: Institute of Surgical Research and Hospital Management; University of Basel ; Basel, Switzerland.
authors.forename: Giandomenica
authors.initials: G
authors.lastname: Iezzi
authors.affiliation: Institute of Pathology; University of Basel ; Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Department of Surgery; Massachusetts General Hospital; Harvard Medical School ; Boston, MA USA.
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
keywords: ADCC, antibody dependent cellular cytotoxicity; BC, breast cancer; CD8 T cell; CRC, colorectal carcinoma; CTL, cytotoxic T lymphocytes; DC, dendritic cells; FGFR, fibroblast growth factor receptor; GIST, gastrointestinal stromal tumor; HCC, hepatocellular carcinoma; HLA, human leukocyte antigen; IDO, indoleamine-2, 3-dioxygenase; IFNγ, interferon γ; IRB, Institutional Review Board; LFA-1, lymphocyte function-associated antigen-1; MHC, the major histocompatibility complex; MICA/B, the major histocompatibility complex (MHC) Class I polypeptide-related sequence A/B; MMPs, matrix metalloproteinases; NK cell; NK, natural killer; PGE2, prostaglandin E2; RCC, renal cell carcinoma; ROC, receiver operating characteristics; TAMs, tumor-associated macrophages; TGF-β1, transforming growth factor β1; TILs, tumor-infiltrating lymphocytes; colorectal carcinoma; cooperation; lymphocyte; survival; tumor