Association between soluble immune mediators and tumor responses in patients with nonsmall cell lung cancer treated with anti‐PD‐1 inhibitor

Abstract

Although programmed death (PD)‐1 immune checkpoint therapies target the immune system, the relationship between inflammatory factors and the clinical outcome of anti‐PD‐1 therapy for nonsmall cell lung cancer (NSCLC) is not fully understood. Here we examined the association between soluble immune mediators and the outcome of treatment with PD‐1 inhibitors in patients with advanced/recurrent NSCLC. In two independent cohorts, we assessed the levels of 88 different soluble immune mediators in peripheral blood before and after anti‐PD‐1 treatment, and evaluated their associations with clinical outcomes. In the training cohort, the plasma levels of chitinase 3‐like‐1 and GM‐CSF before treatment (p = 0.006 and p = 0.005, respectively) and changes in the plasma levels of CXCL2, VEGF, IFNα2, and MMP2 after treatment (p < 0.001, p = 0.019, p = 0.019, and p = 0.012, respectively) were significantly correlated with PFS. The change in the plasma CXCL2 level was also significantly associated with treatment‐related AEs (p = 0.017). In the validation cohort, however, only the changes in the plasma levels of CXCL2 and MMP2 after treatment were associated with PFS (p = 0.003 and p = 0.006, respectively), and these changes were maintained during the course of anti‐PD‐1 therapy in patients who showed better clinical outcomes, even in those with tumor pseudoprogression. Since CXCL2 and MMP2 can be easily measured by minimally invasive blood sampling, they could be useful for monitoring of clinical outcomes in NSCLC patients receiving PD‐1 inhibitor therapy.

Prognostic value of YKL-40 in solid tumors: a meta-analysis of 41 cohort studies

“…In total, 461 studies were further excluded because of there was YKL-40 protein in the tumor tissue, the study was meta-analysis, the study involved leukemia or lymphoma, there were multiple publications, there was insufficient data, there was no survival data or the data was not relevant to tumor tissues. Finally, 41 articles [9, 18–57] met the selection criteria after reviewing the abstracts or full texts.

Fig. 1The literature search and study selection process

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Impact of pseudoprogression and treatment beyond progression on outcome in patients with non-small cell lung cancer treated with immune checkpoint inhibitors

“…This is similar to the incidence of PsP in NSCLC patients from prior studies, ranging from 0.6% to 6.9%. 10,[16][17][18][19][20][21] However, in previous studies, the definition and criteria to evaluate PsP have not been standardized. Unlike prior immune response criteria such as irRC and irRECIST, iRECIST has adopted the new concept of the "reset."…”

Leucine rich repeat LGI family member 3: Integrative analyses reveal its prognostic association with non‑small cell lung cancer

“…All LGI3-regulated and NSCLC-altered genes were found in the previous literature on NSCLC that reported an association of genetic variations, expression and function of these genes with NSCLC. Expression levels of PTGS2 (26), IL6 (27), CCL2 (28), NCF1/2 (29), CXCL2 (30), CSF3 (31), CXCL13 (32), LPL (33), SERPINE1 (34), PPARG (35) and FABP4 (36), and the promoter methylation of DLK1 (37) have been reported to be associated with the prognosis and pathogenesis of NSCLC. A total of seven genes (PTGS2, IL6, CCL2, NCF2, CXCL2, CSF3 and NCF1) that have been reported to be increased by LGI3 may be downregulated in NSCLC due to the suppression of LGI3 expression.…”