The Toll/IL-1 receptor (TIR) domain of TLRs, found in the majority of TLRs including the ones downregulated in our CRC cohort, in association with myeloid differentiation primary-response protein 88 (MyD88), is responsible for downstream signaling including NF-kB activation and inflammatory cytokine induction to illicit an adaptive immune response [31]. The gene discussed is NFKB1; the disease is colorectal carcinoma.