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NK cells and T cells cooperate during the clinical course of colorectal cancer.

  • Sconocchia G Laboratory of Tumor Immunology and Immunotherapy; Institute of Translational Pharmacology; CNR , Rome, Italy.
  • Eppenberger S Institute of Pathology; University of Basel ; Basel, Switzerland.
  • Spagnoli GC Institute of Surgical Research and Hospital Management; University of Basel ; Basel, Switzerland.
  • Tornillo L Institute of Pathology; University of Basel ; Basel, Switzerland.
  • Droeser R Institute of Surgical Research and Hospital Management; University of Basel ; Basel, Switzerland.
  • Caratelli S Laboratory of Tumor Immunology and Immunotherapy; Institute of Translational Pharmacology; CNR , Rome, Italy.
  • Ferrelli F Institute of Systems Medicine; University of Rome "Tor Vergata" ; Rome, Italy.
  • Coppola A Institute of Systems Medicine; University of Rome "Tor Vergata" ; Rome, Italy.
  • Arriga R Institute of Systems Medicine; University of Rome "Tor Vergata" ; Rome, Italy.
  • Lauro D Institute of Systems Medicine; University of Rome "Tor Vergata" ; Rome, Italy.
  • Iezzi G Institute of Surgical Research and Hospital Management; University of Basel ; Basel, Switzerland.
  • Terracciano L Institute of Pathology; University of Basel ; Basel, Switzerland.
  • Ferrone S Department of Surgery; Massachusetts General Hospital; Harvard Medical School ; Boston, MA USA.
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  • 2015-01-23
Published in:
  • Oncoimmunology. - 2014
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
English 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.
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  • English
Open access status
bronze
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https://sonar.ch/global/documents/232774
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