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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2010-02, Vol.59 (2), p.203-213
• Main Authors: Lipoldova, Marie, Havelkova, Helena, Badalova, Jana, Vojtiskova, Jarmila, Quan, Lei, Krulova, Magdalena, Sohrabi, Yahya, Stassen, Alphons P, Demant, Peter
• Format: Article
• Language: English
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-009-0739-y

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 IFNg in allogeneic mixed lymphocyte cultures (MLC). We found that IFNg production by lymphocytes of O20/A mice is lower than by lymphocytes of OcB-9/Dem mice (both H2 super( pz )) stimulated in MLC by irradiated splenocytes of C57BL/10SnPh (H2 super( b )) or BALB/cHeA (H2 super( d )) mice, or by ConA. IFNg production in MLCs of individual (O20OcB-9)F sub(2) mice stimulated by irradiated C57BL/10 splenocytes and genotyped for microsatellite markers revealed four IFNg-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.