**3. Clinical applications of Immunoscore**

Immunoscore has been tested to be a prognostic marker that surpasses the TNM staging. Pages et al. concluded that patients with high Immunoscore had the lowest risk of recurrence and longest survival. In his study, only 5% of the patients with high Immunoscore had a recurrence at 3 years, 87% of the patients reached the overall survival at 3 years, and 82% of the patients reached 5-year overall survival [14].

There is a possible association between MSI status and immune cell infiltrates. MSI-high tumors have intraepithelial T cells due to expression of neo-antigens on the cell surface, and this could be the reason why this kind of tumors had better prognosis [15].

Comparing to the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM classification system, the Immunoscore classification seems to be superior as prognostic tool. For all patients with CRC stages I/II/III, multivariate Cox analysis revealed that the immune criteria remained highly associated with prognosis [16]. Wirta et al. concluded that a lower Immunoscore was associated with increasing AJCC/UICC stage, as well as with increasing T stage, presence of lymph node, distant metastasis, and perineural or lymphovascular invasion [17].

One day the classification of cancer will have a new component, TNM-I (immune).

Additionally, Immunoscore can predict the response to treatment and could be a biomarker that helps clinicians to decide what patients must have chemotherapy. Morris et al. concluded that high TIL is predictive of response to chemotherapy with 5-fluorouracil [18], and Viaud et al. revealed that cyclophosphamide induces a TH17 and TH1 antitumor response, making the tumors resistant to this chemotherapy [19].
