PMC9870311_01
Comparison of the biomarkers for immune checkpoint inhibitors (ICIs) therapy between MSI-H altered and wt groups. (A) Heatmap of immune related scores in MSI-H altered and wt groups. (B-D) The boxplot indicated Teff IFN-gamma, CYT, and MERK 18 signature were reduced in MSI-H wt group. (E-G) The boxplot indicated the higher innate PD-1 resistance (IPRES) gene signature, EMT and TGF Beta in MSI-H wt group. (H, I) The boxplot indicated the higher the expression of immune checkpoints CD274 and PDCD1 in MSI-H altered group.
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TPM3-NTRK1 (T9:N9,  Supplementary Figure 6 ) fusion and the MSI-H phenotype, with no germline or somatic aberration in MMR genes ( Figure 7B ).
Clinical response of an ICIs-treated NRKT fusion MSI-H CRC patient. (A) Diagram of the course of disease management, showing different treatment regimens prescribed. (B) The molecular diagnosis of this case. (C) IHC staining of PD-L1 expressions in tumor proportion score (TPS), combined positive score (CPS), positive control (PC), and negative control (NC). (D) CT evaluation and HE images of the patient at the first (upper) and second (lower) surgical timepoint. (E) Comparison of MLH1 methylation levels between NRKT fusion MSI-H tumor tissue and non-tumor tissue. T, tumor tissue; N, non-tumor tissue.
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We presented an MSI-H CRC case harboring NTRK1 fusion who received anti-PD-1 treatment and achieved a durable response ( Figure 7A ). TPM3-NTRK1 (T9:N9,  Supplementary Figure 6 ) fusion and the MSI-H phenotype, with no germline or somatic aberration in MMR genes ( Figure 7B ). The expression of PD-L1 was detected by IHC staining ( Figure 7C ). Tumors (RECIST) version 1.1 after 4 cycles but with decreasing tumor serum marker carcinoembryonic antigen (CEA). The patient underwent surgical resection in March 2020. The postoperative pathological specimens showed extensive granulomatous inflammation with tissue necrosis, multinucleated giant cells, and no tumor cells observed, which was evaluated as pathological complete response (pCR) ( Figure 7D ). The methylation status of MLH1p in the tumor tissue of this case and the corresponding adjacent tissue were tested ( Figure 7E ).