Cancer Types | Biomarkers | Samples | Cell types | Cell numbers | Main findings | Immunotherapy | Location | Ref. |
---|---|---|---|---|---|---|---|---|
Melanoma | TCF7 expression of CD8+ T cells | N = 48 melanoma tumor tissues | CD8+ T cells | 6,350 | Higher levels of TCF7 protein in CD8+ T cells at baseline predict better responses to ICB therapy. | Anti-PD-1, anti-CTLA-4 | Tumor | [108] |
TNBC | CXCL13+ CD8+ T cells, CXCL13+ CD4+ T cells, and MMP9+ macrophages | N = 78 TNBC tumor tissues and blood samples | CD45+ cells | 489,490 | The baseline levels of CXCL13+ CD8+ T cells, CXCL13+ CD4+ T cells, and MMP9+macrophages are high in patients responding to PD-L1 blockade immunotherapy. | Atezolizumab | Tumor | [109] |
NSCLC | PD1+ CXCL13+ T cells, IgG+ plasma cells, and SPP1+ macrophages | N = 35 NSCLC samples and N = 29 matched normal tissues | CD45+ cells | 361,929 | The lung cancer activation module (LCAM) includes PD1+ CXCL13+ T cells, IgG+ plasma cells, and SPP1+ macrophages. A high baseline LCAM score is a biomarker of a favorable ICB response. | Atezolizumab | Tumor | [110] |
GC | CXCL13 expression in CD8+/CD4+ T cells | N = 19 GC samples and N = 19 normal tissues | T cells | 53,768 | CXCL13+ CD8+ and CD4+ T cells are important for TLS formation and high CXCL13 expression is associated with improved efficacy of ICB. | Pembrolizumab | Tumor | [111] |
NSCLC | Tissue-resident memory CD8+ T (TRM)-like cells | N = 10 NSCLC patients | CD45+ cells | 31,887 | The high expression signature of CD8+ ITGAE+ TRM-like cells with high cytotoxicity, effector signature, and memory signature is predictive of favorable anti-PD-1 therapy responses. | Anti-PD-1 | Tumor | [129] |
Melanoma and NSCLC | TOX expression of T cells | N = 17 melanoma tumors and N = 14 NSCLC tumors | CD8+ T cells | 3,195 | TOX is specifically expressed by T cells and is a key transcription factor regulating T cell exhaustion. Lower expression of TOX in tumor-infiltrating T cells predicts a better response to anti-PD-1 therapy. | Nivolumab, pembrolizumab | Tumor | [113] |
Multiple cancers | TSTR cells | N = 486 samples | T cells | 308,048 | TSTR cells exhibited high expression of heat-shock genes and stress response signatures. TSTR cells are more abundant in non-responsive tumors. | Anti-PD-1, anti-PD-L1, anti-CTLA-4 | Tumor | [114] |
Bladder cancer | Cytotoxic CD4+ T cells | N = 7 bladder cancer patients | CD4+ T cells | 19,842 | The signature genes of cytotoxic CD4+ T cells include ABCB1, APBA2, SLAMF7, GPR18, and PEG10. High expression of this signature is associated with a positive response to PD-1 blockade. | Atezolizumab | Tumor | [130] |
NSCLC | Plasma cells | N = 44 NSCLC patients | CD79A+ B cells | 20,362 | High levels of intratumoral plasma cells at baseline predict a favorable response to PD-L1 blockade therapy. | Atezolizumab | Tumor | [115] |
Melanoma | CD69+ B cells and IGLL5− CD69+ B cells | N = 43 melanoma tumor tissues | B cells | N.A. | The fractions of CD69+ B cells and IGLL5− CD69+ B cells at baseline are both higher in responders to ICB therapy. And a higher expression level of the TLS signature predicts a better prognosis after ICB. | Anti-PD-1, anti-CTLA-4 | Tumor | [116] |
NSCLC | FCRL4+ FCRL5+ memory B cells and CD16+ CX3CR1+ monocytes | N = 15 NSCLC tumor tissues | All the cells | 92,330 | High signatures of FCRL4+ FCRL5+ B cells and CD16+ CX3CR1+ monocytes in the TME predict a positive response to ICB therapy. | Anti-PD-1 | Tumor | [131] |
Melanoma | TREM2high macrophages | N = 48 melanoma tumor tissues | CD45+ cells | 16,291 | High levels of TREM2high macrophages at baseline are associated with poor clinical responses to ICB therapy. | Anti-PD-1, anti-CTLA-4 | Tumor | [117] |
NSCLC | TREM2+ TAMs | N = 26 NSCLC tumor tissues and blood samples | All the cells | 50,483 | High levels of TREM2+ TAMs at baseline predict poor clinical responses to immunotherapy. | Anti-PD-1 | Tumor | [118] |
HCC | APOC1 | N = 8 HCC tumor and normal tissues and blood samples | CD45+ cells | 212,494 | APOC1 is over-expressed in TAMs of HCC tissues and is negatively correlated with PD-1 and PD-L1 expression. High levels of APOC1 predict unfavorable responses to anti-PD-1 therapy. | Anti-PD-1 | Tumor | [119] |
PDAC | LRRC15+ CAFs | N = 20 normal and PDAC mice, N = 22 PDAC patients | Dataset1: PDPN+ stromal cells Dataset2: CAFs | Dataset1: 13,454 Dataset2: 8,931 | TGF-β driven LRRC15+ CAFs increase with tumor progression and higher expression of LRRC15+ CAFs signature is predictive of worse clinical response to atezolizumab in several human cancers. | Atezolizumab | Tumor | [85] |
Breast cancer | ecm-myCAFs and TGFβ-myCAFs | N = 7 breast cancer tissues | FAPhi CD29med − hi SMAhi CAFs | 18,296 | CAF subsets with high expression of genes encoding extracellular matrix proteins and TGF-β signaling pathway are respectively termed ecm-myCAFs and TGFβ-myCAFs. High levels of ecm-myCAFs and TGFβ-myCAFs predict primary resistance to ICB in several cancer types. | Pembrolizumab, nivolumab | Tumor | [86] |
PDAC | meCAFs | N = 16 PDAC tumor tissues and normal pancreatic samples | CAFs | 8,439 |  A new CAF subset exhibiting highly activated metabolic signatures and high expression of PLA2G2A and CRABP2 is termed meCAFs. High levels of meCAFs at baseline predict a positive response to immunotherapy. | Anti-PD-1 | Tumor | [120] |
HNSCC | tsCAFs | N = 8 HNSCC tumor tissues | CAFs | 5,414 | Two CAF subsets (HNCAF-0/3) that can prevent exhaustion and enhance the cytotoxicity of CD8+ T cells are together termed T-cell stimulating CAF (tsCAF). High levels of tsCAF signatures at baseline predict favorable responses to ICB therapy. | Nivolumab, pembrolizumab | Tumor | [121] |
Multiple cancers | TaNK cells | N = 1,223 samples | NK cells | 160,011 | An NK cell subset (CD56dimCD16hi c6-DNAJB1) with low cytotoxicity and high stress response is termed tumor-associated NK (TaNK) cells. TaNK cell signatures predict resistance to ICB. | N.A. | Tumor | [122] |
Melanoma | SIRPA expression of melanoma cells | N.A. | All the cells | N.A. | Melanoma cells interact with CD8+ T cells via the SIRPα/CD47 axis to increase CD8+ T cell cytotoxicity. Higher expression of SIRPA is predictive of a better response to ICB therapy in melanoma. | Anti-PD-1, anti-PD-L1 | Tumor | [123] |
Melanoma | Toxicity and large count number of CD8+ T cells | N = 16 blood samples | CD8+ T cells | 22,445 | Patients whose CD8+ T cells have lower toxicity and fewer expanded clones may have worse responses to ICB therapy. | Pembrolizumab, nivolumab, ipilimumab | Blood | [124] |
Melanoma | MAIT cells | N = 183 blood samples from 20 patients | CD3+ CD8+ T cells | 51,701 |  A high proportion of MAIT cells in peripheral blood at baseline predicts a favorable response to anti-PD-1 therapy. | Nivolumab, pembrolizumab | Blood | [125] |
Melanoma | S100A9+ monocytes | N = 16 blood samples | PBMCs | ~ 50,000 | High levels of baseline S100A9+ monocytes in peripheral blood predict poor clinical responses to ICB therapy. | Nivolumab | Blood | [127] |
Melanoma | CD8+ TOXPHOS cells | N = 16 melanoma tumor tissues and blood samples | CD8+ T cells | 173,061 |  A unique CD8+ T cell subset with high levels of oxidative phosphorylation (OXPHOS), high exhaustion markers, and high cytotoxicity markers is termed CD8+ TOXPHOS. High CD8+ TOXPHOS cell signatures in tumors and peripheral blood predict ICB resistance. | N.A. | Blood and tumor | [126] |
CRC | Inflammatory conditions and neutrophil-to-lymphocyte ratio (NLR) | N = 6 MSI-H CRC tumor samples | All the cells | 12,118 | Neutrophils participate in immunosuppression via the CD80/CD86-CTLA4 axis. A high NLR is predictive of an unfavorable ICB response in MSI-H CRC patients. | Anti-PD-1 | Blood and tumor | [128] |