Table 2.
Biomarkers for irAEs.
| Biomarkers | Cancer type | Patient number | Treatment | Key data and clinical significance | References | Evidence level |
|---|---|---|---|---|---|---|
| Body composition parameters | Melanoma | 84 | Ipilimumab | Both sarcopenia and low MA were independent factors associated with high-grade irAEs. | Daly et al. (151) | 2b |
| Sex | Melanoma | 140 | Ipilimumab | Females were associated with higher rates of irAEs. | Valpoine et al. (152) | 2b |
| IL-6 | IL-6 at baseline was negatively associated with irAE. | |||||
| Melanoma | 26 | Ipilimumab | Lower circulating IL-6 was significantly correlated with higher incidences of colitis-related irAEs. | Chaput et al. (57) | 2b | |
| Melanoma | 15 | Nivolumab | Increases in circulating IL-6 after treatment were significantly associated with development of irAEs. | Tanaka et al. (37) | 4 | |
| IL-17 | Melanoma | 35 | Ipilimumab | Circulating IL-17 levels at baseline correlated with the incidence of grade 3 irAEs of diarrhea/colitis, indicating that increased levels of circulating IL-17 may be reflective of patients with subclinical colitis. | Tarhini et al. (153) | 2b |
| Soluble CD163, CXCL5 | Melanoma | 46 | Nivolumab | The absolute change rate of soluble CD163 and CXCL5 after initial treatment was increased in patients with irAEs compared to those without irAEs. | Fujimura et al. (154) | 2b |
| Blood cell counts | Melanoma, RCC, urothelial carcinom | 167 | Anti-PD-1 antibodies | Absolute lymphocyte and eosinophil numbers at baseline and 1 month after initial treatment were independent factors associated with a higher incidence of irAEs of grade ≥2. | Diehi et al. (155) | 2b |
| Melanoma | 44 | Anti-PD-1 antibodies | Both baseline absolute eosinophil count and relative eosinophil count at 1 month significantly correlate with the occurrence of endocrine irAEs. | Nakamura et al. (45) | 2b | |
| Melanoma | 101 | Nivolumab | An increase in total WBC count and a decrease in relative lymphocyte count plus increase in relative neutrophil count on the same day of, or just prior to irAE occurrence were associated with development of lung or gastrointestinal irAEs. | Fujisawa et al. (156) | 2b | |
| autoantibodies | Melanoma, NSCLC | 168 | Nivolumab | TSH and TPOAb were associated with higher incidence of thyroid irAEs. | Kimbara et al. (157) | 2b |
| Solid cancer including melanoma, NSCLC, RCC | 27 | Anti-PD-1 antibodies, atezolizumab | Patients positive for type 1 diabetes antibodies at the time of presentation developed diabetes-related irAEs after fewer cycles than those without autoantibodies. | Stamatouli et al. (158) | 2b | |
| T cell repertoire | Prostate cancer | 42 | Ipilimumab plus granulocyte-monocyte colony-stimulating factor | An early increase in diversity and the generation of new T- cell clones correlated with the development of irAEs. | Oh et al. (159) | 2b |
| Gut microbiome | Melanoma | 26 | Ipilimumab | Patients whose baseline microbiota was enriched with the Faecalibaterium genus and other Firmicutes showed a higher incidence of colitis-related irAEs. | Chaput et al. (57) | 2b |
| Melanoma | 34 | Ipilimumab | Increased representation of bacteria belonging to the Bacteroidetes phylum was associated with resistance to development of ipilimumab-induced colitis. | Dubin et al. (160) | 2b |
NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma; irAE, immune-related adverse event; WBC, white blood cell; TPOAb, antithyroid peroxidase antibodies (TPOAb). Evidence level was evaluated based on the following criteria; 1a, systematic review/ meta-analysis of randomized controlled trials; 1b, individual randomized controlled trials; 2a, systematic review/meta-analysis of cohort studies; 2b, individual cohort study; 3a, systematic review/meta-analysis of case-control studies; 3b, individual case-control studies; 4, case series; 5, expert opinions.