RT Journal Article
SR Electronic
T1 Mutant KRAS Promotes NKG2D+ T Cell Infiltration and CD155 Dependent Immune Evasion
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4663
OP 4674
DO 10.21873/anticanres.14465
VO 40
IS 8
A1 KENSUKE NISHI
A1 SHUHEI ISHIKURA
A1 MASAYO UMEBAYASHI
A1 TAKASHI MORISAKI
A1 TAKASHI INOZUME
A1 TETSUSHI KINUGASA
A1 MIKIKO AOKI
A1 SATOSHI NIMURA
A1 ANTHONY SWAIN
A1 YOICHIRO YOSHIDA
A1 SUGURU HASEGAWA
A1 KAZUKI NABESHIMA
A1 TOSHIFUMI SAKATA
A1 SENJI SHIRASAWA
A1 TOSHIYUKI TSUNODA
YR 2020
UL http://ar.iiarjournals.org/content/40/8/4663.abstract
AB Background/Aim: Roles for mutant (mt) KRAS in the innate immune microenvironment in colorectal cancer (CRC) were explored. Materials and Methods: Human CRC HCT116-derived, mtKRAS-disrupted (HKe3) cells that express exogenous mtKRAS and allogenic cytokine-activated killer (CAK) cells were co-cultured in 3D floating (3DF) culture. The anti-CD155 antibody was used for function blocking and immuno histochemistry. Results: Infiltration of CAK cells, including NKG2D+ T cells, into the deep layer of HKe3-mtKRAS spheroids, was observed. Surface expression of CD155 was found to be up-regulated by mtKRAS in 3DF culture and CRC tissues. Further, the number of CD3+ tumor-infiltrating cells in the invasion front that show substantial CD155 expression was significantly larger than the number showing weak expression in CRC tissues with mtKRAS. CD155 blockade decreased the growth of spheroids directly and indirectly through the release of CAK cells. Conclusion: CD155 blockade may be useful for therapies targeting tumors containing mtKRAS.