Abstract
Natural killer (NK) cells play a key role in tumor immune surveillance. However, adoptive immunotherapy protocols using NK cells have shown limited clinical efficacy to date, possibly due to tumor escape mechanisms that inhibit NK cell function. In this study, we analyzed the effect of coculturing melanoma cells and NK cells on their phenotype and function. We found that melanoma cells inhibited the expression of major NK receptors that trigger their immune function, including NKp30, NKp44, and NKG2D, with consequent impairment of NK cell-mediated cytolytic activity against various melanoma cell lines. This inhibitory effect was primarily mediated by indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2). Together, our findings suggest that immunosuppressive barriers erected by tumors greatly hamper the antitumor activity of human NK cells, thereby favoring tumor outgrowth and progression.
| Original language | English |
|---|---|
| Pages (from-to) | 1407-1415 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 72 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Mar 15 2012 |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity. / Pietra, Gabriella; Manzini, Claudia; Rivara, Silvia; Vitale, Massimo; Cantoni, Claudia; Petretto, Andrea; Balsamo, Mirna; Conte, Romana; Benelli, Roberto; Minghelli, Simona; Solari, Nicola; Gualco, Marina; Queirolo, Paola; Moretta, Lorenzo; Mingari, Maria Cristina.
In: Cancer Research, Vol. 72, No. 6, 15.03.2012, p. 1407-1415.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity
AU - Pietra, Gabriella
AU - Manzini, Claudia
AU - Rivara, Silvia
AU - Vitale, Massimo
AU - Cantoni, Claudia
AU - Petretto, Andrea
AU - Balsamo, Mirna
AU - Conte, Romana
AU - Benelli, Roberto
AU - Minghelli, Simona
AU - Solari, Nicola
AU - Gualco, Marina
AU - Queirolo, Paola
AU - Moretta, Lorenzo
AU - Mingari, Maria Cristina
PY - 2012/3/15
Y1 - 2012/3/15
N2 - Natural killer (NK) cells play a key role in tumor immune surveillance. However, adoptive immunotherapy protocols using NK cells have shown limited clinical efficacy to date, possibly due to tumor escape mechanisms that inhibit NK cell function. In this study, we analyzed the effect of coculturing melanoma cells and NK cells on their phenotype and function. We found that melanoma cells inhibited the expression of major NK receptors that trigger their immune function, including NKp30, NKp44, and NKG2D, with consequent impairment of NK cell-mediated cytolytic activity against various melanoma cell lines. This inhibitory effect was primarily mediated by indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2). Together, our findings suggest that immunosuppressive barriers erected by tumors greatly hamper the antitumor activity of human NK cells, thereby favoring tumor outgrowth and progression.
AB - Natural killer (NK) cells play a key role in tumor immune surveillance. However, adoptive immunotherapy protocols using NK cells have shown limited clinical efficacy to date, possibly due to tumor escape mechanisms that inhibit NK cell function. In this study, we analyzed the effect of coculturing melanoma cells and NK cells on their phenotype and function. We found that melanoma cells inhibited the expression of major NK receptors that trigger their immune function, including NKp30, NKp44, and NKG2D, with consequent impairment of NK cell-mediated cytolytic activity against various melanoma cell lines. This inhibitory effect was primarily mediated by indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2). Together, our findings suggest that immunosuppressive barriers erected by tumors greatly hamper the antitumor activity of human NK cells, thereby favoring tumor outgrowth and progression.
UR - http://www.scopus.com/inward/record.url?scp=84858202941&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858202941&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-11-2544
DO - 10.1158/0008-5472.CAN-11-2544
M3 - Article
C2 - 22258454
AN - SCOPUS:84858202941
VL - 72
SP - 1407
EP - 1415
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 6
ER -