Can the CD4+/CD8+ ratio predict the outcome of interferon-alpha therapy for renal cell carcinoma?
BACKGROUND
In a randomised trial, patients with renal cell carcinoma (RCC) treated with vinblastine alone or in combination with interferon-alpha (IFN) were monitored for peripheral blood lymphocyte subsets (CD4+ and CD8+) prior to and during treatment to elucidate the influence of IFN on these cells, and the association of the change in the CD4+/CD8+ ratio with treatment outcome.


METHODS
Blood samples were systematically obtained from 30 patients receiving either vinblastine or vinblastine + IFN-alpha-2a. Flow cytometry was used to detect CD4+ (T-helper) and CD8+ cells (T-suppressor) with monoclonal antibodies.


RESULTS
Increasing CD4+/CD8+ ratios were seen in 10 of 17 patients in the vinblastine-IFN group and in 7 of 13 patients in the vinblastine group. Two of three patients achieving a complete response with the vinblastine-IFN treatment showed a dramatic increase in CD4+/CD8+ ratio concomitantly with regression of all metastases. Those treated with vinblastine-IFN who showed an increasing ratio had a better median survival (not reached at 28 months of follow-up) compared to those with a decreasing ratio (6.3-month survival) (P = 0.0037, log-rank). No such difference occurred in patients treated with vinblastine alone. In the multivariate analysis, the increase in CD4+/CD8+ ratio was the most important prognostic factor.


CONCLUSIONS
In a proportion of patients receiving an interferon-based therapy, IFN seems to influence the host's immune system, resulting in an increased CD4+/CD8+ ratio concomitantly with tumour regression. Changes in the CD4+/CD8+ ratio of patients with metastatic RCC receiving such therapy, may provide valuable prognostic information and a basis for future improvements of immunotherapy.
Hernberg
M
M
Department of Oncology, Helsinki University Central Hospital, Finland.
Muhonen
T
T
Pyrhönen
S
S
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D016516:CD4-CD8 Ratio; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D011994:Recombinant Proteins; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D014747:Vinblastine / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014747:Vinblastine