PMID- 12918068
OWN - NLM
STAT- MEDLINE
DCOM- 20031117
LR  - 20201226
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 106
IP  - 6
DP  - 2003 Oct 10
TI  - Renal cell carcinoma-infiltrating natural killer cells express differential 
      repertoires of activating and inhibitory receptors and are inhibited by specific 
      HLA class I allotypes.
PG  - 905-12
AB  - Among tumor-infiltrating lymphocytes (TILs) directly isolated from renal cell 
      carcinomas (RCCs), we found substantial numbers of natural killer (NK) cells in 
      most tumor tissues. They could be identified reliably in situ with an antibody 
      directed against the activating receptor (AR) NKp46 that is exclusively expressed 
      by all NK cells. NK-enriched TILs (NK-TILs) showed cytotoxicity against major 
      histocompatibility complex (MHC) class I-negative cell lines. The ability to 
      detect lysis of target cells was dependent on the percentage of NK cells within 
      the TILs, and cytotoxicity was only observed after overnight activation with 
      low-dose interleukin-2 (IL-2). Infiltrating NK cells were found to express 
      various inhibitory receptors (IRs); among these the CD94/NKG2A receptor complex 
      was overrepresented compared to the autologous peripheral blood mononuclear cell 
      (PBMC) population. Other IRs were underrepresented, indicating that NK 
      subpopulations vary in their tumor-infiltrating capacity. IRs expressed by 
      NK-TILs are functional since receptor engagement with MHC class I ligands 
      presented by human leukocyte antigen (HLA)-transfected target cell lines was able 
      to inhibit NK-mediated cytotoxicity. NK-TILs were also able to lyse autologous or 
      allogeneic tumor cell lines in vitro. This activity correlated with low HLA class 
      I surface expression since lysis could be inhibited by interferon 
      (IFN)-gamma-expressing RCC transductants that displayed a higher surface density 
      of HLA class I molecules. Therefore, NK cells infiltrating tumor tissues have an 
      inherent ability to recognize transformed cells, but they require cytokine 
      activation and are sensitive to inhibition by IR ligands.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Schleypen, Julia S
AU  - Schleypen JS
AD  - Institute of Molecular Immunology, GSF National Research Center for the 
      Environment and Health, Munich, Germany.
FAU - Von Geldern, Marion
AU  - Von Geldern M
FAU - Weiss, Elisabeth H
AU  - Weiss EH
FAU - Kotzias, Nicole
AU  - Kotzias N
FAU - Rohrmann, Karl
AU  - Rohrmann K
FAU - Schendel, Dolores J
AU  - Schendel DJ
FAU - Falk, Christine S
AU  - Falk CS
FAU - Pohla, Heike
AU  - Pohla H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antigens, CD)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Interleukin-2)
RN  - 0 (Isoantigens)
RN  - 0 (Receptors, Immunologic)
SB  - IM
MH  - Antigens, CD/*metabolism
MH  - Carcinoma, Renal Cell/*immunology/pathology
MH  - Cytotoxicity, Immunologic
MH  - HLA Antigens/*metabolism
MH  - Histocompatibility Antigens Class I/immunology/*pharmacology
MH  - Humans
MH  - Interleukin-2/metabolism
MH  - Isoantigens/immunology/pharmacology
MH  - Kidney Neoplasms/*immunology/pathology
MH  - Killer Cells, Lymphokine-Activated/immunology
MH  - Killer Cells, Natural/*immunology
MH  - Lymphocyte Activation
MH  - *Lymphocytes, Tumor-Infiltrating
MH  - Receptors, Immunologic/metabolism
EDAT- 2003/08/15 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/08/15 05:00
PHST- 2003/08/15 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/08/15 05:00 [entrez]
AID - 10.1002/ijc.11321 [doi]
PST - ppublish
SO  - Int J Cancer. 2003 Oct 10;106(6):905-12. doi: 10.1002/ijc.11321.