Killer immunoglobulin-like receptor (KIR) and KIR-ligand genotype do not correlate with clinical outcome of renal cell carcinoma patients receiving high-dose IL2.
NK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR-ligand interactions. Inhibitory KIR-ligands have been identified as HLA molecules, while activating KIR-ligands are largely unknown. Individuals that have not inherited the corresponding KIR-ligand for at least one inhibitory KIR gene are termed the "KIR-ligand missing" genotype, and they are thought to have a subset of NK cells that express inhibitory KIRs for which the corresponding KIR-ligand is missing on autologous tissue, and thus will not be inhibited through KIR-ligand recognition. In some settings where an anticancer immunotherapeutic effect is likely mediated by NK cells, individuals with a KIR-ligand missing genotype have shown improved clinical outcome compared to individuals with an "all KIR-ligands present" genotype. In addition, patients receiving hematopoietic stem cell transplants for leukemia may do better if their donor has more activating KIR genes (i.e., KIR haplotype-B). In a recent multi-institution clinical trial of patients with metastatic renal cell carcinoma receiving high-dose IL2 (HD-IL2), 25 % of patients showed a complete or partial tumor response to this therapy. We genotyped KIR and KIR-ligand genes for these patients (n = 107) and tested whether KIR/KIR-ligand genotypes correlated with patient clinical outcomes. In these analyses, we did not find any significant association of KIR/KIR-ligand genotype (either KIR-ligand missing or the presence of KIR haplotype-B) with patient outcome in response to the HD-IL2 therapy.
Department of Human Oncology, University of Wisconsin, 4159 WIMR Bldg. UW-Madison Campus, 1111 Highland Avenue, Madison, WI, 53705, USA.
Wei
W
Wang
Department of Human Oncology, University of Wisconsin, 4159 WIMR Bldg. UW-Madison Campus, 1111 Highland Avenue, Madison, WI, 53705, USA.
Amy K
AK
Erbe
Department of Human Oncology, University of Wisconsin, 4159 WIMR Bldg. UW-Madison Campus, 1111 Highland Avenue, Madison, WI, 53705, USA.
Mikayla
M
Gallenberger
Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA.
KyungMann
K
Kim
Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA.
Lakeesha
L
Carmichael
Department of Human Oncology, University of Wisconsin, 4159 WIMR Bldg. UW-Madison Campus, 1111 Highland Avenue, Madison, WI, 53705, USA.
Dustin
D
Hess
Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA.|Department of Pediatrics, University of Wisconsin, Madison, WI, USA.
Eneida A
EA
Mendonca
Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA.
Yiqiang
Y
Song
Department of Human Oncology, University of Wisconsin, 4159 WIMR Bldg. UW-Madison Campus, 1111 Highland Avenue, Madison, WI, 53705, USA.
Jacquelyn A
JA
Hank
Department of Biostatistics, Dana Farber Cancer Institute, Boston, MA, USA.
Su-Chun
SC
Cheng
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Sabina
S
Signoretti
The Cytokine Working Group, Rockville, MD, USA.|Department of Medicine, Georgetown University, Washington, DC, USA.
Michael
M
Atkins
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Alexander
A
Carlson
NCI-Biologic Resources Branch, Frederick, MD, USA.
Jonathan M
JM
Weiss
The Cytokine Working Group, Rockville, MD, USA.|Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
James
J
Mier
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
David
D
Panka
The Cytokine Working Group, Rockville, MD, USA.|Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
David F
DF
McDermott
Department of Human Oncology, University of Wisconsin, 4159 WIMR Bldg. UW-Madison Campus, 1111 Highland Avenue, Madison, WI, 53705, USA. pmsondel@humonc.wisc.edu.|Department of Pediatrics, University of Wisconsin, Madison, WI, USA. pmsondel@humonc.wisc.edu.
Paul M
PM
Sondel
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D005838:Genotype; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D008024:Ligands; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics*
D000970:Antineoplastic Agents; D007376:Interleukin-2; D008024:Ligands; D054340:Receptors, KIR
HLA; High-dose IL2; Killer immunoglobulin-like receptors; NK cells; Renal cell carcinoma
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