Table 1 Nonspecific biomarker of irAEs
From: The biomarkers related to immune related adverse events caused by immune checkpoint inhibitors
Biomarker | Author | Year | Cancer type | Patient number | Treatment | Correlation between biomarker and irAEs | Possible hypothesis |
|---|---|---|---|---|---|---|---|
CRP | Abolhassani AR [18] | 2019 | MM | 37 | Anti-PD-1 Anti-CTLA-4 | CRP elevation can predict the onset of irAEs in patients treated with ICIs in the absence of infectious disease. | Tumor-promoting inflammation could cause a systemic inflammatory response;CRP level was positively associated with the infiltration of CD8 + T cell and Treg cell which could activate the systemic inflammatory response. |
IL-6 | Okiyama N [19] | 2017 | MM | 22 | Anti-PD-1 | The IL-6 level was significantly increased in the patients with psoriasiform dermatitis after nivolumab treatment. | Overactivation of the immune system;Excessive release of inflammatory cytokines. |
Valpione S [15] | 2018 | MM | 140 | Anti-CTLA 4 | A lower baseline level of IL-6 was strongly associated with the development of irAEs. | ||
Blood cell count | Fujisawa Y [20] | 2017 | MM | 101 | Anti-PD-1 | The increase of WBC counts and the decrease of relative lymphocyte counts were closely related to the incidence of grade 3–4 irAEs. | Conventional blood cell counts could be a crude reflection of the body’s immune state, but the mechanism is unclear. |
Diehl A [21] | 2017 | Multiple solid tumors (lung cancer, MM, RCC, urothelial, HNSCC, Merkel cell carcinoma, colon cancer) | 167 | Anti-PD-1 | Higher baseline and increase of absolute lymphocyte and eosinophil counts after ICIs treatment were strongly associated with the development of irAEs. | ||
Nakamura Y [22] | 2019 | MM | 45 | Anti-PD-1 | The elevation of absolute eosinophil count at baseline and relative eosinophil count at 1 month might be valuable biomarkers to predicte endocrine irAEs. | ||
Cytokines | Khan S [23] | 2019 | Multiple solid tumors (lung cancer, kidney cancer, MM, head/neck cancer, liver cancer, bladder cancer) | 65 | Anti-PD-1/L1 Anti-CTLA 4 | The up-regulation of various cytokines after ICIs treatment was closely related to the occurrence of irAEs, especially the induced CXCL9, 10, 11 and 13. | Activate T cell;Excessive release of cytokines;Various cytokines have powerful pro-inflammatory activities, including stimulating immune cell recruitment, proliferation, survival, differentiation, and effector functions, and many of these cytokines (such as IL-1A, IL-1B, IL-2, IFN 2, and IL-12P70) are associated with inflammation, which is the basis of autoimmune diseases. |
Lim SY [24] | 2019 | MM | 98 | Anti-PD-1 Anti-CTLA 4 | Eleven cytokines, including G-CSF, GMCSF, Fractalkine, FGF-2, IFN-2, IL-12p70, IL-1a, IL-3 1B, IL-1RA, IL-2, IL-13, were significantly upregulated in patients with severe irAEs at baseline and early during treatment. | ||
TMB | Bomze D [25] | 2019 | Multiple solid tumors | 16,397 | Anti-PD-1 | There is a significant positive correlation between high TMB and irAEs during anti-PD-1 therapy in a variety of solid tumors | While fighting against neoantigens, T cells could also cross-react with the corresponding wild-type antigens in normal tissues, resulting in damage to normal tissues. |
sCLTA-4 | Pistillo MP [26] | 2018 | MM | 113 | Anti-CTLA-4 | Higher baseline levels of sCTLA-4 were closely associated with irAEs, especially the gastrointestinal adverse events. | Elevated levels of sCTLA-4 might block the interactions between full-length CTLA-4 expressed by autoreactive T cells and Tregs as well as B7 ligands, thus enhance the cytotoxicity of T cells and reduce the immunosuppression function of Treg cell. |