ONCOmmunity

Mutant KRAS Promotes NKG2D⁺ T Cell Infiltration and CD155 Dependent Immune Evasion.

By: Kensuke Nishi, Shuhei Ishikura, Masayo Umebayashi, Takashi Morisaki, Takashi Inozume, Tetsushi Kinugasa, Mikiko Aoki, Satoshi Nimura, Anthony Swain, Yoichiro Yoshida, Suguru Hasegawa, Kazuki Nabeshima, Toshifumi Sakata, Senji Shirasawa, Toshiyuki Tsunoda

Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
2020-05-23; doi: 10.21873/anticanres.14465

Abstract

Background/aim

Roles for mutant (mt) KRAS in the innate immune microenvironment in colorectal cancer (CRC) were explored.

Materials

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.