Effect of blood transfusion during radiotherapy on the immune function of patients with cancer of the uterine cervix: role of interleukin-10.
OBJECTIVE
To analyze prospectively the effects of blood transfusion administered during radiotherapy (RT) on the immune function of patients with locally advanced cervical cancer.


METHODS
In a total of 15 patients, 7 transfused and 8 untransfused, lymphocyte populations, including CD3+, CD4+, and CD8+ T-cell subsets, B cells (CD19+), and natural killer (NK) cells (CD56+, CD16+, CD3-) were studied before (i.e., time 0), during (i.e., times 1 and 2), and after (i.e., time 3) therapy. Expression of the early (CD25) and late (HLA-DR) activation markers on CD3+ T cells, the intracellular levels of perforin in CD8+ and CD56+ cells, and interferon (IFN)-gamma, interleukin (IL)-2, and IL-4 in CD4+ and CD8+ T cells were also measured. NK cell cytotoxicity against the NK-sensitive target K-562 cells and CD8+ T-cell-directed cytotoxicity against OKT3 hybridoma cells were also assessed. Finally, the plasma levels of the immunoregulatory cytokine IL-10 were analyzed by enzyme-linked immunosorbent assay.


RESULTS
The mean absolute number of all lymphocyte subsets compared with pretreatment levels decreased significantly during RT of both transfused and untransfused patients (p >0.001), with no detectable differences between the two groups in terms of total lymphocytes or relative numbers of CD3+ and CD4+ T cells, CD56+ NK cells, or CD19+ B cells. In contrast, concomitant with an inversion of the CD4/CD8 ratio, a significant increase in the number of CD8+ T cells at time 2 and CD3+ T cells, CD8+ T cells, and NK cells at time 3 was found in the transfused patients compared with the untransfused group. The percentages of CD25+/CD3+ T cells and HLA-DR+/CD3+ T cells increased during RT of the untransfused patients, but CD3+ T cells showed decreased CD25 expression and increased HLA-DR expression in the transfused group. An increase of CD8+ IFN-gamma+ T cells with a concomitant decrease in CD8+ IL-2+ T cells was found in the transfused vs. untransfused group, and no differences were noted in the percentage of CD4+ IFN-gamma+ T cells and CD4+ IL-2+ T cells. The proportion of perforin-positive CD8+ and CD56+ cells was higher in the transfused group than in the untransfused group. However, CD56+ cells and CD8+ T cells from the transfused patients showed markedly diminished cytotoxic function. Finally, IL-10 was detected only in the plasma of the transfused patients.


CONCLUSIONS
Blood transfusion during primary RT for cervical cancer profoundly alters the magnitude and characteristics of radiation-induced immunosuppression. Elevated serum IL-10 in transfused patients may play a role in the disregulation of lymphocyte function, in particular, the depression of NK- and T-cell cytotoxicity. Investigation of alternatives to blood transfusion during RT that do not diminish host immunity is warranted.
Santin
Alessandro D
AD
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA. santinalessandrod@uams.edu
Bellone
Stefania
S
Palmieri
Michela
M
Bossini
Barbara
B
Dunn
Donna
D
Roman
Juan J
JJ
Pecorelli
Sergio
S
Cannon
Martin
M
Parham
Groesbeck P
GP
D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000097:blood; D001402:B-Lymphocytes / Q000378:metabolism; D001803:Blood Transfusion; D017252:CD3 Complex / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019002:CD56 Antigen / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D007694:Killer Cells, Natural / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011878:Radiotherapy / Q000379:methods*; D017452:Receptors, IgG / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000097:blood; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000532:radiotherapy*
D018941:Antigens, CD19; D017252:CD3 Complex; D019002:CD56 Antigen; D016207:Cytokines; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2; D054353:Perforin; D016753:Interleukin-10