Significant impairment in immune recovery after cancer treatment.
BACKGROUND
Although immunosuppression from cancer adjuvant therapy has been documented, how these suppressed immune responses recover to baseline values after completion of cancer adjuvant therapy has not been studied systematically.


OBJECTIVE
The objective of this study was to examine the probability of immune recovery after cancer adjuvant therapy and the potential impact of cancer adjuvant therapy type and cancer stage on immune recovery in patients with newly diagnosed breast cancer.


METHODS
In a repeated-measures design, immune responses were measured four times in 80 patients with early-stage breast cancer: before and at 2, 6, and 12 months from the beginning of cancer adjuvant therapy. Natural killer cell activity, lymphokine-activated killer cell activity, lymphocyte proliferation, CD subsets (CD4, CD8, and CD56), and cytokines (interferon-gamma, interleukin [IL]-2, IL-4, IL-6, and IL-1alpha) were selected for their relevance to breast cancer. Immune recovery was defined by the level of immune response reaching to and above baseline levels. Data were analyzed using a multivariate generalized linear mixed-model approach.


RESULTS
Delayed immune recovery to pretreatment baseline levels continued to the 12-month time point in all parameters. The percentages of immune recovery ranged from 6% to 76% of the patients, varying among immune parameters. Overall, immune recovery was poorer for interferon-gamma, IL-2, IL-4, lymphocyte proliferation, and natural killer cell activity than was for CD subsets and IL-6. The type of cancer adjuvant therapy, not cancer stage, showed selective influence on immune recovery. Chemotherapy or chemotherapy and radiotherapy combination significantly delayed IL-2 recovery, whereas radiotherapy significantly delayed IL-4 recovery.


CONCLUSIONS
Immune recovery after breast cancer adjuvant therapy is delayed significantly for an extended time period in numerous immune parameters. The type of cancer adjuvant therapy has selective influence on immune recovery. Future investigations are warranted to elucidate the time course of immune recovery, clinical significance of poor immune recovery, and factors influencing immune recovery to develop potential interventions.
Kang
Duck-Hee
DH
School of Nursing, University of Alabama at Birmingham, Birmingham, AL 35294, USA. kangd@uab.edu
Weaver
Michael T
MT
Park
Na-Jin
NJ
Smith
Barbara
B
McArdle
Traci
T
Carpenter
John
J
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000532:radiotherapy; D015704:CD4 Antigens / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D053582:Interleukin-1alpha / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D016014:Linear Models; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D015999:Multivariate Analysis; D020127:Recovery of Function; D015144:Southeastern United States; D013997:Time Factors
D015704:CD4 Antigens; D019002:CD56 Antigen; D016827:CD8 Antigens; D053582:Interleukin-1alpha; D007376:Interleukin-2; D015850:Interleukin-6; D015847:Interleukin-4; D007371:Interferon-gamma