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CRC.ImmunotherapyResponseTest: colorectal cancer immunotherapy response test

In colorectal cancer, MSI/MSS status is widely used as the biomarker of whether a colorectal cancer patient should receive anti-PD1. But ~50% of MSI colorectal cancer patients do not respond to anti-PD1, and some MSS colorectal cancer patients benefit from anti-PD1. MSI/MSS status does not fully explain response/resistance to anti-PD1 in colorectal cancer. Other biomarkers, TMB and PDL1, are also often used. These biomarkers(MSI, TMB, PDL1) share the same notion that they directly/indirectly measure the likelihood of high neoantigen level or high CD8+ T cell infiltration, but not other characters of the tumor microenvironment.

Carbon Logic Biotech CRC.ImmunotherapyResponseTest is a molecular diagnostic test for colorectal cancer patients. CRC.ImmunotherapyResponseTest analyze colorectal-cancer-specific signatures of CD8+ T cell infiltration and CD8+ T cell exhaustion states in the tumor microenvironment. CRC.ImmunotherapyResponseTest has 2 functions:

(1) Identify a subgroup ~10% of MSS colorectal cancer patients that can potentially benefit from anti-PD1(Figure 1, blue box of Anti-PD1 row): as the number of MSS patients is much larger than MSI patients, this result means that CRC.ImmunotherapyResponseTest can identify ~20% more colorectal cancer patients who can potentially benefit from anti-PD1.

(2) Identify anti-PD1 resistance subtypes of MSI colorectal cancer patients: ~50% of MSI nonresponders show terminal exhaustion of CD8+ T cells, and ~50% of MSI nonresponders show insufficient amount of tumor infiltrating CD8+ T cells. Treatment of 2 different subtypes of MSI anti-PD1 nonresponders need to be designed differently.

Figure 1. CRC.ImmunotherapyResponseTest across 454 colorectal cancer samples

Figure 2. CRC.ImmunotherapyResponseTest showed predivtive values in 3 anti-PD1 treated patients cohorts (HR=4.59, pvalue=0.056(Figure 2A); HR=2.12, pvalue=0.115(Figure 2B); HR=5.04, pvalue=0.003(Figure 2C); p.combine=0.0007).

Figure 2A.
Figure 2B.
Figure 2C.

Sun Tian, Fulong Wang, Rongxin Zhang, Gong Chen. (2021) Global pattern of CD8+ T cell infiltration and exhaustion in colorectal cancer predicts cancer immunotherapy response. Frontiers in Pharmacology. DOI: 10.3389/fphar.2021.715721. PMID: 34594218