Heterozygosity Or Homozygosity For 2 HLA Class II Haplotypes Predict Favorable Outcomes For Renal Cell Carcinoma Treated With Cytokine Therapy

Abstract

We conclude that heterozygosity or homozygosity for the class II haplotypes DRB1*0301/DQA1*0501/DQB1*0201 and DRB1*1501/DQA1*0102/DQB1*0602 is associated with durable response and survival in patients with metastatic renal cell carcinoma treated with cytokine therapy.

Genetic Deficiency of Complement Isoforms C4A or C4B Predicts Improved Survival of Metastatic Renal Cell Carcinoma

“…This concept also predicts that RCC patients who are genetically predisposed to autoimmunity are more likely to respond to immunotherapy and enjoy prolonged survival. Supporting this paradigm, we have reported significantly improved survival for stage IV RCC patients, treated with immunotherapy, who carry autoimmunity-associated HLA class II haplotypes 4. Mechanistically, there are two explanations for our findings: the first is optimal tumor antigen presentation by these class II molecules; the second is genetic linkage of the true effector mechanism to these class II haplotypes.…”

“…The strongest survival benefit was associated with any combination of the two DQA1 alleles (*0102/*0501, *0501/*0501, or *0102/*0102) 4. Because the C4 gene, in the mid-MHC region, is in the vicinity of the HLA class II locus, multivariate analysis was performed to determine if the survival benefit provided by a relative C4 isoform deficiency was independent of the presence of these autoimmune class II haplotypes.…”

“…Informed consent was obtained from all individuals. The study population was derived from the same 80 patient cohort included in our previous report4, of which 61 individuals had sufficient DNA remaining to complete the present study.…”

Data Mining for Identification of Molecular Targets in Ovarian Cancer

“…The lowest differences were observed in NMOT (N=28) Figure 1-2. Moreover, eight genes were the most significant and integrated to specific signaling pathways and they are related to cancer: FGF4 in breast (Saint-Ruf et al, 1990;Schmitt et al, 1996), colorectal (Ikeda et al, 2008), melanoma (Adelaide et al, 1988), stomach (Ikeda et al, 2008) and ovarian cancer (Schmitt et al, 1996;Mayr et al, 2006); ITGA11 in kidney (Dalgliesh et al, 2010), laryngeal (Stransky et al, 2011) and lung (Young et al, 2009; MHC class ll alpha chain in non-small cell lung carcinoma (Ohri et al, 2009); HLA-DQA1 in hepatocellular carcinoma (Donaldson et al, 2001), renal cell carcinoma (Ellerhorst et al, 2003), melanoma (D'Alessandro et al, 1987;Nagore et al, 2002;Ugurel et al, 2004); C1QTNF5 is associated to adrenocortical carcinoma (Fonseca et al, 2012), endometrial and lung neoplasms.…”