Tumor MHC class I expression alters cancer-associated myelopoiesis driven by host NK cells.
J Immunother Cancer
; 10(10)2022 10.
Article
en En
| MEDLINE
| ID: mdl-36283735
ABSTRACT
Downregulation of MHC class I (MHCI) molecules on tumor cells is recognized as a resistance mechanism of cancer immunotherapy. Given that MHCI molecules are potent regulators of immune responses, we postulated that the expression of MHCI by tumor cells influences systemic immune responses. Accordingly, mice-bearing MHCI-deficient tumor cells showed reduced tumor-associated extramedullary myelopoiesis in the spleen. Depletion of natural killer (NK) cells abrogated these differences, suggesting an integral role of immune-regulatory NK cells during tumor progression. Cytokine-profiling revealed an upregulation of TNF-α by NK cells in tumors and spleen in mice-bearing MHCI expressing tumors, and inhibition of TNF-α enhanced host myelopoiesis in mice receiving adoptive transfer of tumor-experienced NK cells. Our study highlights a critical role of NK cells beyond its identity as a killer lymphocyte and more importantly, the potential host responses to a localized tumor as determined by its MHCI expression.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Mielopoyesis
/
Neoplasias
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
J Immunother Cancer
Año:
2022
Tipo del documento:
Article
País de afiliación:
Suecia