Abstract 2343: Immunogenetics of cancer and aging

Abstract

Antigen altered idiotype regulates specific immune responses (Cell Immunol. 1978: 4). Mendelian segregation of a given +/- phenotype defines an immune response gene (Benacerraf, Nobel). Autoimmunity producing anti-self clones must be eliminated or specifically suppressed, so a large portion of the antigenic repertoire resembles allogeneic MHC molecules (Medawar, Nobel). We proposed that exposure to many different allogeneic HLA molecules could cause specific immune suppression within the repertoire of epitopes and that these blank spots or in the universe of target eventually would overlap with specificities including targets for eliminating pathogens such as viruses or tumor antigens. Some holes become large enough to result in an acquired immunodeficiency syndrome (AIDS) The opposite is also possible (Allogeneic Effect, Transplant Rev. 1972, 12; 141). This requires viable cells and cytokines released by host and/or donor. IR-genes for tumor resistance localize to the MHC. Class I/II MHC genes (Cancer Res. 1982; 35:1586) and NK cell receptor ligands (J. Stem Cell Res. 2007), regulate adaptive and innate immunity. We examined the combination of HLA specificities and the alleles of ligands of receptors of NK cells in breast cancer patients, HIV non progressors, and centenarians in Mexico. Immunological evaluation (CD4+,CD8+,CD19+ & NK cells and quantitative IgM, IgG, & IgA in breast cancer (BCA) patients in California. Overall survival (OS) depended on specificities (idiotypes) and the regulation of innate and adoptive immunity. The BCA patients and centenarians did not have HIV infection. People with more CD4 cells, more NK cells and more IgG, survive longer than those with the opposite immune profile. The immune specificity repertoire has evolved to avoid fatal autoimmunity, all orchestrated by T regs via T-cell antigen receptors and variable regions of Ig. The antigen receptors (CAR-T) and Ig variable region antigen receptors (Jerne, Nobel) are idiotypes, Single amino acid (AA) changes become altered antigens of the history of the patient: environment (e.g., microbiome), vaccination (e.g., BCG ), and virus infections (Sendai or CMV in mice, HIV and/or others like HPV in man). This is true for single AA changes in both mice (H-2 mutants) and man; NK cell receptor ligands (Thr v Met). The results show profound effects on survival. Data, including MHC and NK receptor ligand phenotypes, OS and immunological evaluation of patients/people will be presented. Immunogenetic profiles of cancer survivors and long lived individuals are similar to those of HIV long term non progressors. Our data support our Immunogenetic Theory of Cancer and Aging. Citation Format: RMichael Williams, Edmond J. Yunis. Immunogenetics of cancer and aging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2343.