Inflammation biomarkers in cancer: mechanistic drivers, diagnostic innovations, and future clinical horizons.
Chronic inflammation is a universally acknowledged characteristic of cancer, playing the role of a vital catalyst in cancer initiation and progression, and a chief predictor of the success or failure of cancer therapies. About 20% of all cancer cases are associated with states of chronic inflammation, and an even greater percentage of cancer cases exploit states of smoldering inflammatory microenvironments for cancer progression, immune escape, angiogenesis, and metastasis. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), a systematic scoping review of literature indexed in Scopus was conducted to assess the potential value of inflammatory biomarkers in cancer diagnostics, prognosis, and therapy. The vital molecular players, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and combined hematological markers including the neutrophil-to-lymphocyte ratio (NLR) and the systemic immune-inflammation index (SII), together with the long-established erythrocyte sedimentation rate (ESR), accurately represent the complex balance between cancer-promoting inflammation and tumor-inhibitory immunity. Critically, these mediators do not render tumors immunologically quiescent. They intensify inflammation while simultaneously engaging negative-feedback circuits - regulatory T-cell expansion via TNF receptor 2, myeloid-derived suppressor cell recruitment, and adenosine-mediated suppression - that produce an inflamed but T-cell-non-responsive phenotype refractory to checkpoint blockade. High levels of systemic inflammation at baseline significantly impair the efficacy of immune checkpoint inhibitors and conventional chemotherapies, via complex pathways including nuclear factor kappa-B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) signaling, metabolic rewiring, and T-cell exhaustion. A direct comparison of assay cost, turnaround, and reported effect sizes indicates that routinely available indices capture much of the prognostic signal attributed to costlier multiplex cytokine panels, although published thresholds vary widely between cohorts and require prospective validation before clinical implementation. Integration of systemic inflammatory biomarkers into clinical practice guidelines is likely to offer a non-invasive and cost-effective strategy for patient stratification and disease monitoring. The use of precision medicine approaches that combine anti-inflammatory therapies such as anti-IL-6 or NOD-like receptor protein 3 (NLRP3) inhibition with immunotherapies is poised to revolutionize the management of therapeutic resistance. Future clinical practice guidelines must focus on the integration of multi-omics and artificial intelligence to address the complex biological and inter-patient and sex differences in the inflammatory tumor microenvironment.