Effects of combined aerobic and resistance training on the inflammatory profile of children with overweight/obesity: A randomized clinical trial.

BACKGROUND: We assessed the effects of a 20-week combined (aerobic and resistance) exercise training programme on the inflammatory profile of prepubertal children with overweight or obesity. METHODS: Totally 109 participants (10.1 ± 1.1 years, 41% girls) were randomly allocated to an exercise or control group. Adiponectin, C-reactive protein, epidermal growth factor, insulin-like growth factor-1, interleukin (IL)-1ß, IL-6, leptin, tumour necrosis factor-α and vascular endothelial growth factor A (VEGFA) were analysed in plasma. Total white blood cell (WBC) count and immune subpopulations (eosinophils, basophils, neutrophils, lymphocytes and monocytes) were also determined. RESULTS: No intervention effect was found for any of the analysed biomarkers (all p ≥ 0.05). We observed a significant sex by intervention interaction for IL-1ß (p = 0.03). When stratifying the sample by sex, the exercise programme induced a significant effect on IL-1ß levels (mean Z-score difference, 0.66 [95% confidence interval 0.32-1.01]) in girls, but not in boys. A lower number of girls in the exercise group showed a meaningful reduction in IL-1ß (i.e., ≥0.2 standard deviations) than in the control group (15% vs. 85%, p = 0.01). CONCLUSIONS: This exercise programme failed to improve the inflammatory profile in prepubertal children with overweight/obesity. Future studies should explore the effect of longer exercise interventions and in combination with diet.

Intensity Matters: Effect of Different Work-Matched Efforts on Subsequent Performance in Cyclists.

PURPOSE: To assess the effect of 2 work-matched efforts of different intensities on subsequent performance in well-trained cyclists. METHODS: The present study followed a randomized controlled crossover design. Twelve competitive junior cyclists volunteered to participate (age, 17 [1] y; maximum oxygen uptake, 71.0 [4.7] mL·kg-1·min-1). The power-duration relationship was assessed through 2-minute, 5-minute, and 12-minute field tests under fresh conditions (control). On subsequent days and following a randomized order, participants repeated the aforementioned tests after 2 training sessions matched for mechanical work (∼15 kJ/kg) of different intensities (ie, a moderate-intensity continuous-training [60%-70% of critical power; CP] session or a session including high-intensity intervals [3-min repetition bouts at 110%-120% of the CP interspersed by 3-min rest periods]). RESULTS: A significantly lower power output was found in the 2-minute test after the high-intensity training session compared not only with the control condition (-8%, P < .001) but also with the moderate-intensity continuous-training session (-7%, P = .003), with no significant differences between the latter conditions. No significant differences between conditions were found for the remaining tests. As a consequence, the high-intensity training session resulted in significantly lower W' values compared to both the control condition (-27%, P = .001) and the moderate-intensity continuous-training session (-26%, P = .012), with no differences between the 2 latter conditions and with no differences for CP. CONCLUSION: A session including high-intensity intermittent efforts induces a greater fatigue, particularly in short-duration efforts and W', than a work-matched continuous-training session of moderate intensity.

Physical exercise: a polypill against chronic kidney disease.

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management.

Exercise is also medicine for iron homeostasis.

High-intensity interval training (HIIT) is gaining popularity as an effective exercise modality to improve cardiometabolic health. Combining high-throughput/sensitivity proteome analyses in subcutaneous adipose tissue with biochemical blood measures, Larsen et al. recently provided mechanistic insights into a potential beneficial role of this exercise modality on iron homeostasis at the whole-body level.

Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.

Lifestyle and cardiovascular risk in working young adults: insights from a nationwide Spanish cohort.

INTRODUCTION AND OBJECTIVES: This study aimed to describe the cardiovascular risk profile of working young adults from Spain and its association with lifestyle. METHODS: Participants (18-30 years) were recruited from a nationwide cohort of economically active adults insured by a large occupational risk prevention company, with data obtained from routine medical assessments. The participants were categorized as having an "unhealthy" cardiovascular risk profile based on the presence of prediabetes/diabetes, prehypertension/hypertension, or hypercholesterolemia, or a "healthy" profile if these conditions were completely absent. The association with lifestyle factors (weight, physical activity, sleeping characteristics, alcohol consumption, smoking) was assessed. RESULTS: A total of 78 421 young adults (27±2 years, 36% female) were evaluated at baseline. The "unhealthy" cardiovascular risk profile was prevalent (18%) and inversely associated (OR, 0.64; 95%CI, 0.57-0.80) with an optimal lifestyle (normal weight, regular physical activity, no drinking/smoking, and good sleep). The latter condition was found in only 3.5% of the participants. On the other hand, prospective analyses in 44 776 participants (median follow-up=2 [range 2-5] years) showed that 2.0% transitioned from a "healthy" to an "unhealthy" profile. Being physically active (OR, 0.95; 95%CI, 0.81-0.99) and having a normal weight (OR, 0.61; 95%CI, 0.51-0.70) were associated with a lower likelihood of this transition. No consistent associations were found for other lifestyle factors. CONCLUSIONS: The prevalence of cardiovascular risk factors is high in economically active young Spanish adults. An unhealthy cardiovascular risk profile is inversely associated with an optimal lifestyle, but the latter is highly infrequent in this population.

The effect of physical exercise on anticancer immunity.

Regular physical activity is associated with lower cancer incidence and mortality, as well as with a lower rate of tumour recurrence. The epidemiological evidence is supported by preclinical studies in animal models showing that regular exercise delays the progression of cancer, including highly aggressive malignancies. Although the mechanisms underlying the antitumorigenic effects of exercise remain to be defined, an improvement in cancer immunosurveillance is likely important, with different immune cell subtypes stimulated by exercise to infiltrate tumours. There is also evidence that immune cells from blood collected after an exercise bout could be used as adoptive cell therapy for cancer. In this Perspective, we address the importance of muscular activity for maintaining a healthy immune system and discuss the effects of a single bout of exercise (that is, 'acute' exercise) and those of 'regular' exercise (that is, repeated bouts) on anticancer immunity, including tumour infiltrates. We also address the postulated mechanisms and the clinical implications of this emerging area of research.

Aortic Diameters and Calcifications in Former World-Class Cyclists.

PURPOSE: Concerns on whether athletes--particularly older ones--are at an increased risk of pathological aortic dilation exist, and the prevalence of aortic calcifications in these individuals is unknown. We aimed to compare the dimensions, distensibility, and prevalence of calcifications in the thoracic aorta between former male professional cyclists (cases) and sex/age-matched controls. METHODS: We used a retrospective cohort design, where cases were former finishers of at least one Grand Tour (Tour de France, Giro d' Italia or Vuelta a España) and controls were untrained individuals with no previous sports history and free of cardiovascular risk. All participants underwent magnetic resonance and computer tomography assessments for the measurement of aortic dimensions and calcifications, respectively. RESULTS: Cases showed larger ( P < 0.05) dimensions than controls for aortic annulus, sinus, and arch, as well as for ascending and descending aorta. However, none of the participants presented with pathological aortic dilation (all diameters <40 mm). A slightly higher prevalence of calcifications in the ascending aorta was observed in cases (13% vs 0% in controls, P = 0.020). Subanalyses confirmed that cases who were still competing (masters category, n = 8) had larger aortic diameters ( P < 0.05) and a greater presence of calcifications in the ascending/descending aorta (38% vs 0% for both segments, P = 0.032) than those who had become inactive ( n = 15). No between-group differences were found for aortic distensibility. CONCLUSIONS: Former professional cyclists, particularly those who are still competing after retirement, show enlarged aortic diameters (albeit without exceeding upper limits of normality). Former professional cyclists also showed a slightly higher prevalence of calcifications in the ascending aorta than controls, although aortic distensibility was not compromised. The clinical relevance of these findings should be the subject of future studies.

Combined exercise intervention in a mouse model of high-risk neuroblastoma: effects on physical, immune, tumor and clinical outcomes.

Background: Exercise might exert anti-tumoral effects in adult cancers but this question remains open in pediatric tumors, which frequently show a different biology compared to adult malignancies. We studied the effects of an exercise intervention on physical function, immune variables and tumoral response in a preclinical model of a highly aggressive pediatric cancer, high-risk neuroblastoma (HR-NB). Methods: 6-8-week-old male mice with orthotopically-induced HR-NB were assigned to a control (N = 13) or exercise (5-week combined [aerobic+resistance]) group (N = 17). Outcomes included physical function (cardiorespiratory fitness [CRF] and muscle strength), as well as related muscle molecular indicators, blood and tumor immune cell and molecular variables, tumor progression, clinical severity, and survival. Results: Exercise attenuated CRF decline (p=0.029 for the group-by-time interaction effect), which was accompanied by higher muscle levels of oxidative capacity (citrate synthase and respiratory chain complexes III, IV and V) and an indicator of antioxidant defense (glutathione reductase) in the intervention arm (all p≤0.001), as well as by higher levels of apoptosis (caspase-3, p=0.029) and angiogenesis (vascular endothelial growth factor receptor-2, p=0.012). The proportion of 'hot-like' (i.e., with viable immune infiltrates in flow cytometry analyses) tumors tended to be higher (p=0.0789) in the exercise group (76.9%, vs. 33.3% in control mice). Exercise also promoted greater total immune (p=0.045) and myeloid cell (p=0.049) infiltration within the 'hot' tumors, with a higher proportion of two myeloid cell subsets (CD11C+ [dendritic] cells [p=0.049] and M2-like tumor-associated macrophages [p=0.028]), yet with no significant changes in lymphoid infiltrates or in cirulating immune cells or chemokines/cytokines. No training effect was found either for muscle strength or anabolic status, cancer progression (tumor weight and metastasis, tumor microenvironment), clinical severity, or survival. Conclusions: Combined exercise appears as an effective strategy for attenuating physical function decline in a mouse model of HR-NB, also exerting some potential immune benefits within the tumor, which seem overall different from those previously reported in adult cancers.

Obesity, cardiovascular risk, and lifestyle: cross-sectional and prospective analyses in a nationwide Spanish cohort.

AIMS: To assess whether overweight and obesity are independently associated with cardiometabolic health [as categorized based on the presence/absence of cardiovascular disease (CVD) risk factors (diabetes, hypercholesterolaemia, or hypertension)], and the role of lifestyle on this association. METHODS AND RESULTS: A nationwide cohort of Spanish adults (18-64 years) was studied using a cross-sectional design and prospective observational design. Lifestyle-related factors (physical activity, sleeping characteristics, alcohol drinking, and smoking) were registered, and participants were classified as having an 'unhealthy' or 'healthy' cardiometabolic status attending to the presence or absence, respectively, of ≥1 CVD risk factor. A number of 596 111 participants (44 ± 9 years, 67% male) were studied at baseline, with prospective analyses in a subcohort [n = 302 061; median follow-up, 2 years (range, 2 to 5)]. Compared to normal weight, overweight and obesity were associated with a higher prevalence [odds ratio, 1.67 (95% confidence interval, 1.61-1.67) and 2.70 (2.69-2.78), respectively] and incidence [1.62 (1.59-1.67) and 2.70 (2.63-2.78)] of an unhealthy cardiometabolic status. Meeting physical activity guidelines reduced the odds of an unhealthy cardiometabolic status at baseline [0.87 (0.85-0.88)] among individuals with overweight/obesity, as well as of transitioning from a healthy status to an unhealthy status during the follow-up [0.87 (0.84-0.94)]. No significant associations were found for the remainder of lifestyle factors. CONCLUSION: Overweight and obesity are independently associated with an unhealthy cardiometabolic status. Regular physical activity attenuates not only the prevalence but also the incidence of CVD risk factors.

This study (n = 596 111, with 302 061 participants followed for ∼2 years) indicates that overweigh and obesity are independently associated with the prevalence and incidence of major cardiovascular disease (CVD) risk factors (hypertension, diabetes, and hypercholesterolaemia). Individuals with metabolically healthy overweight/obesity are more likely to develop CVD risk factors in the short-to-middle term than their peers with normal weight even after accounting for lifestyle. Regular physical activity is the only lifestyle factor that seems to be inversely and independently associated with the prevalence and incidence of the studied CVD risk factors among individuals with overweight/obesity.

Effects of physical exercise on physical function in older adults in residential care: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Physical exercise is effective at attenuating ageing-related physical decline in general, but evidence of its benefits for older adults in residential care, who often have functional dependency, multimorbidity, and polypharmacy, is inconclusive. We aimed to establish the effects of exercise interventions on the physical function of this population. METHODS: For this systematic review and network meta-analysis, we searched PubMed, Web of Science, Cochrane Library, Rehabilitation & Sports Medicine Source, and SPORTDiscus to identify randomised controlled trials assessing the effects of exercise interventions (vs usual care) on physical function (ie, functional independence, physical performance, and other related measures, such as muscle strength, balance, or flexibility) in adults aged 60 years or older living in residential care. Relevant studies published in English or Spanish up to Jan 12, 2023, were included in the systematic review. The quality of studies was assessed using the Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX) score. A network meta-analysis was performed for physical function-related outcomes reported in at least ten studies, with subanalyses for specific intervention (ie, exercise type, training volume, and study duration) and participant (eg, having cognitive impairment or dementia, pre-frail or frail status, and being functionally dependent) characteristics. The study protocol was registered on PROSPERO (CRD42021247809). FINDINGS: 147 studies (11 609 participants, with mean ages ranging from 67 years [SD 9] to 92 years [2]) were included in the systematic review, and were rated as having overall good quality (median TESTEX score 9 [range 3-14]). In the meta-analysis (including 105 studies, n=7759 participants), exercise interventions were associated with significantly improved overall physical function, with a standardised mean difference [SMD] of 0·13 (95% credible interval [CrI] 0·04-0·21), which was confirmed in all analysed subpopulations. The strongest association was observed with 110-225 min per week of exercise, and the greatest improvements were observed with 170 min per week (SMD 0·36 [95% CrI 0·20-0·52]). No significant differences were found between exercise types. Subanalyses showed significant improvements for almost all analysed physical function-related outcomes (Barthel index, five-times sit-to-stand test, 30-s sit-to-stand test, knee extension, hand grip strength, bicep curl strength, Short Physical Performance Battery, 6-min walking test, walking speed, Berg balance scale, and sit-and-reach test). Large heterogeneity was found between and within studies in terms of population and intervention characteristics. INTERPRETATION: Exercise interventions are associated with improved physical function in older adults in residential care, and should, therefore, be routinely promoted in long-term care facilities. FUNDING: None. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Physical Exercise and the Hallmarks of Breast Cancer: A Narrative Review.

Growing evidence suggests that, among the different molecular/cellular pathophysiological mechanisms associated with cancer, there are 14 hallmarks that play a major role, including: (i) sustaining proliferative signaling, (ii) evading growth suppressors, (iii) activating invasion and metastasis, (iv) enabling replicative immortality, (v) inducing angiogenesis, (vi) resisting cell death, (vii) reprogramming energy metabolism, (viii) evading immune destruction, (ix) genome instability and mutations, (x) tumor-promoting inflammation, (xi) unlocking phenotypic plasticity, (xii) nonmutational epigenetic reprogramming, (xiii) polymorphic microbiomes, and (xiv) senescent cells. These hallmarks are also associated with the development of breast cancer, which represents the most prevalent tumor type in the world. The present narrative review aims to describe, for the first time, the effects of physical activity/exercise on these hallmarks. In summary, an active lifestyle, and particularly regular physical exercise, provides beneficial effects on all major hallmarks associated with breast cancer, and might therefore help to counteract the progression of the disease or its associated burden.

Pre-sleep protein supplementation in professional cyclists during a training camp: a three-arm randomized controlled trial.

Background: The effects of pre-sleep protein supplementation on endurance athletes remain unclear, particularly whether its potential benefits are due to the timing of protein intake or solely to an increased total protein intake. We assessed the effects of pre-sleep protein supplementation in professional cyclists during a training camp accounting for the influence of protein timing. Methods: Twenty-four professional U23 cyclists (19 ± 1 years, peak oxygen uptake: 79.8 ± 4.9 ml/kg/min) participated in a six-day training camp. Participants were randomized to consume a protein supplement (40 g of casein) before sleep (n = 8) or in the afternoon (n = 8), or an isoenergetic placebo (40 g of carbohydrates) before sleep (n = 8). Indicators of fatigue/recovery (Hooper index, Recovery-Stress Questionnaire for Athletes, countermovement jump), body composition, and performance (1-, 5-, and 20-minute time trials, as well as the estimated critical power) were assessed as study outcomes. Results: The training camp resulted in a significant (p < 0.001) increase in training loads (e.g. training stress score of 659 ± 122 per week during the preceding month versus 1207 ± 122 during the training camp), which induced an increase in fatigue indicators (e.g. time effect for Hooper index p < 0.001) and a decrease in performance (e.g. time effect for critical power p = 0.002). Protein intake was very high in all the participants (>2.5 g/kg on average), with significantly higher levels found in the two protein supplement groups compared to the placebo group (p < 0.001). No significant between-group differences were found for any of the analyzed outcomes (all p > 0.05). Conclusions: Protein supplementation, whether administered before sleep or earlier in the day, exerts no beneficial effects during a short-term strenuous training period in professional cyclists, who naturally consume a high-protein diet.

Durability in Professional Cyclists: A Field Study.

PURPOSE: To assess durability in professional cyclists, as well as potential associated indicators. METHODS: Twelve male professional cyclists participated in the study (age: 26 [5] y, VO2max: 83.0 [3.6] mL·kg-1·min-1). They performed a 20-minute time trial (TT) on 2 different sessions separated by a 48-hour period: (1) with no previous fatigue (TTFresh) and (2) immediately after a long submaximal ride (approximately 4 h, 40 kJ/kg) (TTFatigue). We then assessed the decay (in percentage) in mean power output (PO) from TTFresh to TTFatigue and its association with different laboratory-based endurance indicators (ventilatory threshold, peak PO, and VO2max) determined through a previous maximal incremental cycling test, as well as with training loads during the 4 weeks preceding the TTs. RESULTS: While no differences were noted in the average heart rate (177 [7] vs 176 [6] beats·min-1, P = .118), there was a significant decay in PO between TTFresh and TTFatigue (386 [29] W vs 375 [28] W [-2.9%], respectively; P = .007), albeit with signs of interindividual variability (range = -8.5% to 1.1%; coefficient of variation = 105%). No significant associations were found between the PO decay and any of the analyzed indicators (all P > .05). CONCLUSIONS: Performance is significantly impaired after a certain amount of work completed (approximately 40 kJ·kg-1) in professional cyclists, and the magnitude of this impairment seems to be not related to "traditional" laboratory-based endurance indicators or to markers of training load. These findings might support the need for specifically assessing durability in cyclists and confirming potential determinants of this parameter.

Diabetes, Hypertension, and the Mediating Role of Lifestyle: A Cross-Sectional Analysis in a Large Cohort of Adults.

INTRODUCTION: Whether diabetes is associated with hypertension risk remains controversial, potentially owing to the confounding effect of lifestyle. This study aims to analyze the association between diabetes and hypertension in adults and the mediating impacts of lifestyle. METHODS: A cohort of Spanish workers (aged 18-64 years) insured by an occupational risk prevention company participated in this nationwide cross-sectional study between 2012 and 2016 (data analysis was performed in 2021). Participants' lifestyle‒related factors-BMI, sleeping hours, alcohol, smoking, and physical activity-were assessed, and the prevalence of hypertension and diabetes was registered. RESULTS: A total of 451,157 participants (33.1% women, aged 44.5 [SD=9.2] years, 3.2% with diabetes, and 29.3% with hypertension) with complete data for all variables were assessed. Having diabetes was associated with a higher prevalence of hypertension even after adjusting for all lifestyle-related factors (OR=1.44, 95% CI=1.43, 1.48), and people with diabetes and hypertension had a higher prevalence of mild kidney function impairment than people with diabetes alone (OR=1.06, 95% CI=1.01, 1.13). However, people with diabetes and an optimal lifestyle-normal weight and sleeping hours, absent-to-little alcohol drinking, nonsmoking, and regular physical activity-presented a prevalence of hypertension comparable with that of those without diabetes (OR=1.00, 95% CI=0.71, 1.32). In separate analyses among people with diabetes, an optimal lifestyle was associated with a lower prevalence of hypertension than the worse-opposite-lifestyle (OR=0.29, 95% CI=0.18, 0.53). The lifestyle-related factors showing the strongest inverse association with adjusted risk of hypertension were normal weight (OR=0.49, 95% CI=0.42, 0.53 versus overweight/obesity) and regular physical activity (OR=0.79, 95% CI=0.74, 0.82 versus inactivity). CONCLUSIONS: Diabetes is positively and largely independently associated with hypertension risk. Yet, a healthy lifestyle can attenuate this association.

Exercise Training and Natural Killer Cells in Cancer Survivors: Current Evidence and Research Gaps Based on a Systematic Review and Meta-analysis.

BACKGROUND: Exercise training can positively impact the immune system and particularly natural killer (NK) cells, at least in healthy people. This effect would be of relevance in the context of cancer given the prominent role of these cells in antitumor immunity. In this systematic review and meta-analysis, we aimed to summarize current evidence on the effects of exercise training on the levels and function of NK cells in cancer survivors (i.e., from the time of diagnosis until the end of life). METHODS: Relevant articles were searched in PubMed, Scopus, Web of Science and Cochrane Central Register of Controlled Trials (until January 11, 2022). Randomized controlled trials (RCT) of exercise training (i.e., non-acute) interventions vs usual care conducted in cancer survivors and assessing NK number and/or cytotoxic activity (NKCA) before and upon completion of the intervention were included. Methodological quality of the studies was assessed with the PEDro scale, and results were meta-analyzed using a random effects (Dersimoian and Laird) model. RESULTS: Thirteen RCT including 459 participants (mean age ranging 11-63 years) met the inclusion criteria. Methodological quality of the studies was overall fair (median PEDro score = 5 out of 10). There was heterogeneity across studies regarding cancer types (breast cancer, non-small cell lung cancer and other solid tumors), treatment (e.g., receiving vs having received chemotherapy), exercise modes (aerobic or resistance exercise, Tai Chi, Yoga) and duration (2-24 weeks). No consistent effects were observed for NK number in blood (mean difference [MD]: 1.47, 95% confidence interval [CI] - 0.35 to 3.29, p = 0.113) or NKCA as assessed in vitro (MD: - 0.02, 95%CI - 0.17 to 0.14, p = 0.834). However, mixed results existed across studies, and some could not be meta-analyzed due to lack of information or methodological heterogeneity. CONCLUSIONS: Current evidence does not support a significant effect of exercise training intervention on NK cells in blood or on their 'static response' (as assessed in vitro) in cancer survivors. Several methodological issues and research gaps are highlighted in this review, which should be considered in future studies to draw definite conclusions on this topic.