NKG2D-mediated antitumor activity by tumor-infiltrating lymphocytes and antigen-specific T-cell clones isolated from melanoma patients.
OBJECTIVE
The role of NKG2D receptor in antitumor immunosurveillance has not been completely clarified. We addressed this issue by investigating the involvement of this receptor in tumor-specific immunologic response in melanoma patients.


METHODS
We determined the presence of NKG2D+ T cells among tumor-infiltrating lymphocytes (TIL) of 10 (one primary and 9 metastatic) melanoma samples and the expression of NKG2D ligands (NKG2DL) by these tumor cells. Moreover, the expression of NKG2D was assessed in a panel of antigen-specific T lymphocytes isolated from melanoma patients and the engagement of NKG2D in antitumor activity mediated by these T cells was determined.


RESULTS
TILs located either in the periphery or within the tumor mass of melanoma samples expressed NKG2D and the expression of this receptor by T cells was retained after in vitro culture. However, NKG2DLs were weakly expressed, or not expressed, by most metastatic lesions with only the primary tumor being positive for all these molecules. In contrast, these ligands were expressed, although heterogeneously, by all in vitro established melanoma lines. Moreover, the engagement of NKG2D occurred in antitumor activity by both freshly isolated and in vitro cultured TILs. However, this receptor was involved to a different extent in the antitumor activity of antigen-specific T-cell clones.


CONCLUSIONS
These findings indicate that NKG2D+ T cells have a role in the immunologic response against tumor. Thus, new immunotherapeutic treatments for melanoma patients should be designed aimed at augmenting the NKG2D+ T lymphocyte-mediated immune response.
Maccalli
Cristina
C
Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori, Milan, Italy. maccalli.cristina@hsr.it
Nonaka
Daisuke
D
Piris
Adriano
A
Pende
Daniela
D
Rivoltini
Licia
L
Castelli
Chiara
C
Parmiani
Giorgio
G
D045744:Cell Line, Tumor; D002999:Clone Cells; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D055607:Receptors, Natural Killer Cell; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D019139:Tumor Escape / Q000276:immunology*
D036341:Intercellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell