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BREAST CANCER SURVIVORS EXHIBIT NORMAL T-CELL MOBILIZATION BUT DIVERGENT INTRACELLULAR CYTOKINE EXPRESSIONWITH ACUTE EXERCISE

Abstract

BACKGROUND: Breast cancer (BC) treatment decreases circulating T-cells, with delayed recovery being associated with greater rates of metastasis. Additionally, BC survivors (BCS) may have attenuated responses to acute exercise, with reduced cellular mobilization compared to non-cancer controls. Moreover, the inclusion of functional markers is limited. As such, the purpose of this study was to investigate the effects of acute exercise in BCS and healthy older women (CON) on T-cell counts, frequency, and intracellular cytokine expression. METHODS: Age-matched BCS (n=13, age=57±9) and CON (n=13, age=58±7) performed 45 min of intermittent cycling at 60% peak power output. Blood samples were obtained at rest, immediately (0h) and 1h post-exercise. T-cell counts, frequency, and intracellular cytokine levels were determined with flow cytometry. p<0.05 and p<0.1 were used for main effects and interactions. RESULTS: Independent of time, CON had higher CD3 (+481 cells, 95% CI: 188, 773, p=0.004) and CD4 counts (+376 cells, 95% CI: 135, 618; p=0.005). Independent of group, there were increases in CD3 (+387 cells, 95% CI: 242, 492), CD4 (+199 cells, 95% CI: 101, 297) and CD8 counts (+76 cells, 95% CI: 46, 105; all p<0.001) at 0h which returned to baseline by 1h. CD4 frequency revealed a significant interaction (p=0.047). Both groups decreased similarly at 0h (-4.4%, 95% CI: -7.4, -1.3; p=0.007) while CON increased by 4.5% (95% CI: 0.1, 9.0; p=0.044) at 1h while BCS remained suppressed. The CD8 frequency interaction was also significant (p<0.001). CON was unchanged throughout while BCS increased by 4.9% (95% CI: 2.0, 7.7; p=0.001) at 1h. There was an interaction for CD4 TNFα (p=0.006), where CON increased at 1h (+10.8%, 95% CI: 3.5, 18.2; p=0.005) while BCS tended to decrease (-6.7%, 95% CI: -14.1, 0.8; p=0.079). Similar patterns were seen in CD8 TNFα frequency, although the relationship was not as strong. Lastly, there was a CD4 IFNγfrequency interaction (p=0.081), with CON increasing at 0h (+5.6%, 95% CI: 0.1, 11.0; p=0.045) and remaining constant, while BCS revealed a non-significant decrease at 1h (-3.2%, 95% CI: -8.5, 2.1; p=0.233). CONCLUSIONS: Independent of exercise, BCS had lower CD3 and CD4 T-cell counts compared to healthy older women. Following acute exercise, CD4 frequency experienced the expected decline but with a slower return to baseline levels in BCS. Intracellular cytokine responses to acute exercise appear to be divergent, with lower levels in BCS that may be indicative of reduced functional capacity for T-cell pathogenic responses and infection control.

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