HLA phenotype and cytokine-induced tumor control in advanced renal cell cancer.
BACKGROUND
The natural history of malignancies, the response to cytokine-based therapy and survival of patients may be partly determined by the human leukocyte antigen (HLA) phenotype. Here, we investigated in a retrospective analysis the correlation of the HLA phenotype of 73 prognostic favored patients with advanced renal cell carcinoma to (a) the expected HLA distribution in Caucasians, (b) the susceptibility or resistance to metastatic sites, (c) response to cytokine-based therapy and (d) sustained cytokine-induced effective tumor control.


METHODS
We retrospectively determined the MHC class I and II antigens in patients with metastatic renal cell carcinoma selected by survival. Antigens were serologically typed by standard lymphocytotoxicity techniques. For statistical analysis, we calculated the probability of the presented HLA antigens in correlation to the expected Caucasian HLA phenotypes. An independent confirmation was performed by using the chi-square and two-tailed Fisher's exact test.


RESULTS
Various HLA antigens deviated significantly from the normal distribution in the Caucasian population. HLA.B44 was the only antigen associated (p < 0.01) with the absence of lung and presence of bone metastases, while it did not impact on overall survival or response to therapy. A1 (p < 0.0001, p < 0.002) and B8 (p < 0.009, p < 0.04) alleles were more frequently expressed in responding patients than expected from the normal distribution in Caucasians and that observed in non-responding patients, respectively. The HLA analysis of patients achieving a durable complete remission showed a significantly higher frequency of expression of the A1 and B8 antigens and furthermore of the B14 antigen (p < 0.05).


CONCLUSIONS
Our data underline the pivotal role of the MHC complex in controlling and regulating the cellular immune response in renal cell cancer. We could identify HLA antigens, which correlate with response to cytokine-treatment, with a long-lasting effective tumor control and prolonged overall survival.
Franzke
A
A
Department of Hematology and Oncology, Medizinische Hochschule Hannover, Germany. franzke.anke@mh-hannover.de
Buer
J
J
Probst-Kepper
M
M
Lindig
C
C
Framzle
M
M
Schrader
A J
AJ
Ganser
A
A
Atzpodien
J
J
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000556:secondary; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D005787:Gene Frequency; D006680:HLA Antigens / Q000032:analysis* / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D015993:Life Tables; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D011994:Recombinant Proteins; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D044465:White People
D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D006680:HLA Antigens; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D005472:Fluorouracil