Loci controlling lymphocyte production of interferon gamma after alloantigen stimulation in vitro and their co-localization with genes controlling lymphocyte infiltration of tumors and tumor susceptibility

Marie Lipoldova*, Helena Havelkova, Jana Badalova, Jarmila Vojtiskova, Lei Quan, Magdalena Krulova, Yahya Sohrabi, Alphons P. M. Stassen, Peter Demant

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

Low infiltration of lymphocytes into cancers is associated with poor prognosis, but the reasons why some patients exhibit a low and others a high infiltration of tumors are unknown. Previously we mapped four loci (Lynf1-Lynf4) controlling lymphocyte infiltration of mouse lung tumors. These loci do not encode any of the molecules that are involved in traffic of lymphocytes. Here we report a genetic relationship between these loci and the control of production of IFN gamma in allogeneic mixed lymphocyte cultures (MLC). We found that IFN gamma production by lymphocytes of O20/A mice is lower than by lymphocytes of OcB-9/Dem mice (both H2 (pz) ) stimulated in MLC by irradiated splenocytes of C57BL/10SnPh (H2 (b) ) or BALB/cHeA (H2 (d) ) mice, or by ConA. IFN gamma production in MLCs of individual (O20 x OcB-9)F(2) mice stimulated by irradiated C57BL/10 splenocytes and genotyped for microsatellite markers revealed four IFN gamma-controlling loci (Cypr4-Cypr7), each of which is closely linked with one of the four Lynf loci and with a cluster of susceptibility genes for different tumors. This suggests that inherited differences in certain lymphocyte responses may modify their propensity to infiltrate tumors and their capacity to affect tumor growth.
Original languageEnglish
Pages (from-to)203-213
JournalCancer Immunology Immunotherapy
Volume59
Issue number2
DOIs
Publication statusPublished - Feb 2010

Keywords

  • Genetic control of interferon gamma production
  • Gene mapping
  • Lymphocyte infiltration of tumors
  • Tumor susceptibility

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