RESUMEN
Background: Tumor-promoting inflammation and inflammatory cytokines are linked to immune checkpoint blockade (ICB) resistance. Methods: We assessed the associations between pre-treatment Interleukin-6 (IL-6), Interleukin-8 (IL-8) levels and on-treatment changes in IL-6, IL-8 and C-reactive protein (CRP) with ICB trial end points. Results: 27 studies representing 6,719 patients were included. Low pre-treatment IL-6 levels were associated with improved objective response rate (ORR) (odds ratio (OR) = 0.31 [0.18-0.55]) and better progression-free survival (PFS) (hazard ratio (HR) = 0.59 [0.48-0.72]) and overall survival (OS) [95% confidence interval (CI)] (HR = 0.42 [0.35-0.50]). Low pre-treatment IL-8 levels were associated with improved ORR (OR = 0.47 [0.36-0.61]) and better PFS (HR = 0.65 [0.58-0.74]) and OS (HR = 0.44 [0.39-0.51]). On-treatment decline in CRP was associated with improved ORR (OR = 0.18 [0.11-0.20]), PFS (HR = 0.40 [0.31-0.91]) and OS (HR = 0.48 [0.40-0.58]). Conclusion: Peripheral blood cytokines warrant further evaluation as enrichment and pharmacodynamic biomarkers for strategies targeting tumor-promoting inflammation.
Measuring a substance called C-reactive protein (CRP) in the blood can help predict if cancer treatments that boost the immune system, like immune checkpoint blockers (ICB), will work. CRP levels are increased when there is inflammation in the body, helping cancer cells grow. IL-6 and IL-8 are related blood markers that are more specific to cancer cells and may improve our ability to predict if ICB will effectivity destroy cancer cells. Our study found that having lower levels of IL-6 and IL-8 before treatment and low levels of CRP during treatment might mean patients live longer and respond better to ICB treatments. Measuring IL-6 and IL-8 before treatment and CRP during treatment could help improve how doctors use ICB to treat cancer by managing inflammation that helps cancer grow.