**10. Gene signatures as biomarkers in TNBC**

A number of multiple gene signatures in correlation with TILs have been studied as surrogates of breast cancer immunogenicity. According to immune-related gene expression profiling breast cancer consisted of four categories namely ICR1–4 (immunologic constants of rejection) and these were seen to be associated with survival in a retrospective manner using in-silico analysis. Interestingly, the ICR4 (Th1 helper phenotype) was linked with the upregulation of transcripts like PD-L1, IDO1, PD-1, FOXP3 and CTLA-4 that indicated a better survival among patients, in contrast a negative regulation was showed in disruptions induced by the presence of MAPK components linked with the ICR1, an unfavorable-immune response. A study on mouse models has shown an increased anti-tumor immune response in TNBC patients that was suggested to result by the inhibition of MEK, a molecule of MAPK pathway in combination with PD-1 inhibitor due to which the MHC I and PD-1 expression on Tumor cells increased resulting in apoptosis of cancer cells. Moreover, in TNBC a four gene-signature such as CXCL13, GBP1, SULT1E1 and HLF were shown to represent an upregulation of TILs and enhanced disease free survival among patients, however their predicting response with ICIs needs to be defined [58].
