Table 4 Biomarkers predicting better response to immunotherapy
Biomarker status | Tumor type | N | Immunotherapy | OS (rate) | PFS (rate) | ORR/Impact | References |
|---|---|---|---|---|---|---|---|
dMMR/MSI | CRC, non-CRC (ampullary or cholangiocarcinoma, endometrial, small bowel, gastric) | 11, 9, respectively | Pembrolizumab | 40% | ~ 5 months (20 weeks): 78% | More responsive | [59] |
dMMR/MSI | mCRC | 74 | Nivolumab | 31% | 12 months: 50% | Durable response and disease control | [81] |
dMMR/MSI | mCRC | 119 | Nivolumab + Ipilimumab | 55% | 9 months and 12 months: 76% and 71%, respectively | Durable response and improved efficacy | [83] |
dMMR/MSI | Recurrent GBM | 21 | Nivolumab | NA | NA | Initial and durable response | [114] |
dMMR/MSI | Advanced, metastatic MSI-H/dMMR CRC | 61 in cohort A, 63 in cohort B | Pembrolizumab | mOS: 31.4 months and NR | mPFS: 2.3 months and 4.1 months | 33% (95% CI 21–46%) and 33% (95% CI 22–46%) | [280] |
dMMR/MSI | 27 types of non-CRC | 233 | Pembrolizumab | mOS:23.5 months | mPFS: 4.1 months | 34.3% (95% CI, 28.3–40.8%) | [281] |
dMMR/MSI | CRPC | 11 | Anti-PD-1/PD-L1 | NA | NA | Durable clinical benefit: 45.5% | [282] |
dMMR/MSI | mCRC | 307 | Pembrolizumab | NR | mPFS: 16.5 months | Longer progression-free survival | [283] |
dMMR/MSI (loss of h MSH2 and MSH6) | Chemo-resistant urothelial tract cancer | 1 | Durvalumab | NA | NA | Complete remission | [115] |
dMMR/MSI, high TMB (> 37–41 mutations/Mb) | mCRC | 22 | Pembrolizumab, Nivolumab, Nivolumab/Ipilimumab, Durvalumab/Tremelimumab | NA | mPFS: > 18 months, | Objective response | [95] |
dMMR/pMMR, higher percentages of mucin and PD-L1 expression | mCRC | 26 | Pembrolizumab | NA | NA | Clinical benefit | [195] |
Higher TMB | Metastatic melanoma | 64 | Ipilimumab or Tremelimumab | mOS: 4.4 years | NA | Durable clinical response | [97] |
Higher TMB | NSCLC | 28/22 | Anti-PD-1/PDL1 therapies | NA | mPFS: NR/mPFS: 2.9 months | ORR: 39.3%/ORR: 9.1% | [284] |
Higher IFN-γ signature (IFN-γ, STAT1, CXCL9, CXCL10, IDO, MHCII HLA-DRA, LAG-3) | Metastatic melanoma, GC, HNSCC | 81,33,40 | Pembrolizumab | NA | NA | Higher response rate | [182] |
Higher IFN-γ signature (IFN-γ, PD-L1, LAG-3 and CXCL9) | NSCLC | 30 | Durvalumab | Longer OS | Longer mPFS | Higher response rate | [137] |
Higher IFN-γ signature (LAG-3, PD-L1, IDO) and TIL | mCRC | 19 | Pembrolizumab | NA | NA | Higher response rate | [196] |
Higher IFN-γ signature and PD-L1 expression | Urothelial carcinoma | 265 | Nivolumab | mOS:7 months | NA | ORR:28·4% with PD-L1 expression of 5% or greater, 23·8% with PD-L1 expression of 1% or greater, 16·1% with PD-L1 expression of less than 1% | [134] |
Higher PD-L1 expression and TMB | Metastatic urothelial carcinoma | 310 | Atezolizumab | NA | NA | Significantly improved ORR | [113] |
Higher PD-L1 expression and TMB | Solid tumors across 22 types | > 300 | Pembrolizumab | NA | Longer PFS | Stronger objective response rate | [285] |
PD-L1 positive | SCLC, melanoma or RCC | 296 | Nivolumab | NA | NA | Complete/partial response | [57] |
PD-L1 positive | Melanoma, NSCLC, RCC, CRC, CRPC | 41 | Nivolumab | NA | NA | Objective response and clinical benefit | [112] |
Higher IDO expression and TIL | Advanced melanoma | 82 | Ipilimumab | NA | NA | Better clinical outcome | [135] |
INCR1 knockdown | Mice tumor models | - | CAR-T cell therapy | NA | NA | Enhanced T cell infiltration, significantly reduced tumor growth | [130] |