Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

Abstract

Background. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed. Our aim was to evaluate serum Th1, Th2, and proinflammatory cytokines in two cohorts of SCLC patients before and during treatment with chemotherapy with or without ipilimumab and to correlate them with survival. Patients and methods. Two cohorts of SCLC patients were studied: patients treated with chemotherapy (n = 47), and patients treated with chemotherapy plus ipilimumab (n = 37). Baseline, on-treatment and after-treatment serum samples were evaluated for the presence of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, GM-CSF, and Mip-1alpha using a Luminex assay. Differential changes in cytokines between cohorts were analyzed. Associations between cytokine levels and their changes with overall survival were evaluated. Results. Patients treated with ipilimumab showed a global increase of all cytokines after treatment initiation. A high level of IL-8 at baseline was associated with worse prognosis regardless of treatment. Baseline increased IL-2 levels predicted sensitivity to ipilimumab, while high IL-6 and TNF-alpha predicted resistance. An on-treatment increase in IL-4 levels in patients treated with immune-chemotherapy was associated with a better overall survival.Conclusions. The addition of ipilimumab to standard chemotherapy in SCLC modulates the serum levels of cytokines. Baseline levels and their change over time relate to overall survival. Blood-based biomarkers are convenient for patients, and our results support prospective validation of cytokines as predictive biomarkers for ipilimumab in SCLC. ARTICLE HISTORY

Serum interleukin-6 and C-reactive protein are associated with survival in melanoma patients receiving immune checkpoint inhibition

“…There is a significant body of evidence from small phase II trials suggesting that high levels of both IL-6 and CRP are associated with a poor outcome with ICI, particularly ipilimumab, [36][37][38] but also nivolumab. 24 25 These data support our more extensive experience in the current work derived from three randomized trials in patients with immunotherapy-naïve metastatic melanoma.…”

The associations between cytokine levels and clinical outcomes in critically ill patients after surgery: a retrospective cohort study

“…In recent decades, our knowledge of the biochemical processes underlying critical illness has considerably improved. We realized that cytokines perform important roles in host defense and maintenance of tissue homeostasis; however, abnormal or excessive production of cytokines disrupts these functions, resulting in inflammation and tissue injury [17], and there is strong evidence that cytokines work as important mediators of inflammatory and immunologic diseases and that elevated cytokine levels can contribute to organ dysfunction [18][19][20]. Evidence suggests that cytokines, including IL-8, TNF-a, and IL-10, strongly predict clinical outcome alone or in combination with other variables or widely accepted severity scores [21,22].…”

Inflammation Cytokine Expression and Association With Clinical Outcomes in Critically Ill Patients After Major Surgery: A Retrospective Cohort Study

“…however, abnormal or excessive production of cytokines disrupts these functions, resulting in in ammation and tissue injury [17], and there is strong evidence that cytokines work as important mediators of in ammatory and immunologic diseases and that elevated cytokine levels can contribute to organ dysfunction [18][19][20]. Evidence suggests that cytokines, including IL-8, TNF-a, and IL-10, strongly predict clinical outcome alone or in combination with other variables or widely accepted severity scores [21,22].…”