Single-cell RNA sequencing in cancer research: discovering novel biomarkers and therapeutic targets for immune checkpoint blockade

Sun, Boyu; Xun, Ziyu; Zhang, Nan; Liu, Kai; Chen, Xiangqi; Zhao, Haitao

doi:10.1186/s12935-023-03158-4

Table 2 Summary of studies identifying new therapeutic targets for immunotherapy revealed by scRNA-seq

From: Single-cell RNA sequencing in cancer research: discovering novel biomarkers and therapeutic targets for immune checkpoint blockade

Cancer types	Cell types	Therapeutic targets	Effects	Therapeutic approach	Mechanisms	Ref.
Melanoma	Cancer cells	CDK4/6	Pro-tumor	CDK4/6 inhibitor (palbociclib and abemaciclib)	Cancer cell immune evasion and T cell exclusion	[132]
TNBC	Cancer cells	MUC1-C	Pro-tumor	MUC1-C inhibitor GO-203	Depletion and dysfunction of CD8⁺ T cells	[144]
PDAC	Cancer cells	SLC4A4	Pro-tumor	SLC4A4 inhibitor DIDS	A bicarbonate transporter increasing TME acidity	[133]
NPC	Cancer cells	CD70	Pro-tumor	Anti-CD70 antibody cusatuzumab	Promoting the suppressive function of Tregs via the CD70-CD27 axis	[143]
Melanoma	CD8⁺ T cells	NKG7	Anti-tumor	NKG7 mRNA transfection	Cytotoxic function in CD8⁺ T cells	[137]
COAD and RCC	CD8⁺ T cells	GITR	Anti-tumor	Agonist anti-GITR antibody	A costimulatory receptor	[145]
Melanoma and sarcoma	CD8⁺ T cells, CD4⁺ T cells	BHLHE40	Anti-tumor	–	A transcription factor required for effective ICB therapy	[146]
Glioma	Cancer cells/myeloid cells – CD8⁺ T cells	CLEC2D/CD161	Pro-tumor	Anti-CD161 antibody HP-3G10	Suppressing cytotoxicity and cytokine secretion of T cells	[147]
LR-CHL	CD4⁺ helper T cells – B cells	CXCL13/CXCR5	Pro-tumor	–	Preventing B cell activation and maturation	[148]
Ovarian cancer	NK cells, CD8⁺ T cells	BRD1	Pro-tumor	BRD1 inhibitor BAY-299	Negatively regulating the activity of T cells and NK cells	[149]
Multiple cancers	NK cells	HIF-1α	Pro-tumor	HIF-1α inhibitor	A transcription factor inhibiting the activation of NK cells	[150]
Multiple myeloma	NK cells	ZNF683	Pro-tumor	–	A transcription factor regulating NK cell exhaustion	[151]
Multiple cancers	CD4⁺ Tregs	CCR8	Pro-tumor	ADCC-prone anti-CCR8 nanobody	A marker induced by Treg activation	[152]
Multiple cancers	CD4⁺ Tregs	CD177	Pro-tumor	Anti-CD177 antibody MEM166	Mediating immune suppressive function of Tregs	[153]
ICC	CD4⁺ Tregs	MEOX1	Pro-tumor	–	A transcription factor regulating Treg hyperactivation	[135]
PDAC	T cells – cancer cells	CCL5/SDC1	Pro-tumor	–	Promoting tumor cell migration	[154]
Glioma	TAMs, CD4⁺ Tregs, CD8⁺ T cells	S100A4	Pro-tumor	–	A small calcium-binding protein related to immunosuppression	[134]
Multiple cancers	TAMs	TREM2	Pro-tumor	Anti-TREM2 monoclonal antibody	Associated with immunosuppression	[138]
Multiple cancers	TAMs	APOE	Pro-tumor	APOE inhibitor COG 133TFA	An oncomarker of TAMs associated with M2-TAMs recruitment	[139]
HCC	TAMs	SPP1	Pro-tumor	Anti-SPP1 monoclonal antibody	Inducing the formation of tumor immune barrier by interacting with CAFs	[155]
HCC	TAMs	PPT1	Pro-tumor	PPT1 inhibitor DC661	Associated with the immunosuppressive TME	[156]
GBM	TAMs	Siglec-9	Pro-tumor	–	Inhibiting the activation of CD8⁺ and CD4⁺ T cells	[157]
RCC	TAMs – cancer cells	IL-1β/IL-1R1	Pro-tumor	Anti-IL1β antibody	Mediating adaptive myeloid resistance and cancer cell EMT	[158, 159]
PDAC	CAFs	HIF2	Pro-tumor	HIF2 inhibitor PT2399	Mediating immunosuppression in the TME	[160]
reRCC	CAFs	Gal1	Pro-tumor	Gal1 inhibitor OTX008	An immunosuppressive factor triggering T cell apoptosis	[161]
HCC	CAFs	CD36	Pro-tumor	CD36 inhibitor sulfo-N-succinimidyl oleate (SSO)	Recruiting MDSCs to increase immunosuppression of the TME	[162]
ICC	CD146⁺ vCAFs – cancer cells	IL-6/IL-6R	Pro-tumor	IL-6R neutralizing antibody or IL-6/IL-6R signaling inhibitor	Enhancing ICC malignancy	[84]
Prostate cancer	Arterial TECs – tip TECs	CXCL12/CXCR4	Pro-tumor	CXCR4 inhibitor AMD3100	Triggering neovascularization	[142]
mUC and mRCC	Multiple cells	CXCL8/CXCR2	Pro-tumor	–	Cancer cell growth and metastasis	[136]
CRC	Multiple cells	CD73	Pro-tumor	CD73 inhibitor AB680	A checkpoint enzyme converting extracellular ATP to immunosuppressive adenosine	[140]
Melanoma and myeloma	Multiple cells	GCN2	Pro-tumor	GCN2 inhibitor GCN2iB	Suppressing inflammatory macrophage polarization and promoting cancer cell survival	[163, 164]
Bladder cancer	Multiple cells	CD39	Pro-tumor	CD39 inhibitor sodium polyoxotungstate	Associated with immunosuppression	[141]
Multiple cancers	Multiple cells	IGSF9	Pro-tumor	Anti-IGSF9 antibody	Suppressing T cell activation	[165]

CDK4/6, cyclin-dependent kinase 4/6; TNBC, triple-negative breast cancer; MUC1-C, mucin 1-C type protein; PDAC, pancreatic ductal adenocarcinoma; SLC4A4, solute carrier family 4 member 4; DIDS, 4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid; TME, tumor microenvironment; NPC, nasopharyngeal carcinoma; Tregs, regulatory T cells; NKG7, natural killer cell granule protein-7; COAD, colon adenocarcinoma; RCC, renal cell carcinoma; GITR, glucocorticoid-induced tumor necrosis factor receptor-related protein; BHLHE40, basic helix-loop-helix family member E40; ICB, immune checkpoint blockade; CLEC2D, C-type lectin domain family 2 member D; LR-CHL, lymphocyte-rich classic Hodgkin lymphoma; CXCL13, C-X-C motif chemokine ligand 13; CXCR5, C-X-C chemokine receptor type 5; NK cells, natural killer cells; BRD1, bromodomain-containing protein 1; HIF-1α, hypoxia inducible factor 1 subunit alpha; ZNF683, zinc finger protein 683; CCR8, CC chemokine receptor 8; ADCC, antibody-dependent cell-mediated cytotoxicity; ICC, intrahepatic cholangiocarcinoma; MEOX1, mesenchyme homeobox 1; CCL5, C-C motif chemokine ligand 5; SDC1, syndecan-1; TAMs, tumor-associated macrophages; S100A4, S100 calcium-binding protein A4; TREM2, triggering receptor expressed on myeloid cells 2; APOE, apoprotein E; HCC, hepatocellular carcinoma; SPP1, secreted phosphoprotein 1; PPT1, palmitoylprotein thioesterase 1; GBM, glioblastoma; Siglec-9, sialic acid-binding Ig-like lectin 9; IL-1β, interleukin-1 beta; IL-1R1, interleukin-1 receptor type 1; EMT, epithelial-mesenchymal transition; CAFs, cancer-associated fibroblasts; HIF2, hypoxia-inducible factor-2; reRCC, recurrent renal cell carcinoma; Gal1, Galectin-1; MDSCs, myeloid-derived suppressor cells; IL-6, interleukin-6; IL-6R, IL-6 receptor; TECs, tumor endothelial cells; CXCL12, C-X-C motif chemokine ligand 12; CXCR4, C-X-C chemokine receptor type 4; mUC, metastatic urothelial carcinoma; mRCC, metastatic renal cell carcinoma; CXCL8, C-X-C motif chemokine ligand 8; CXCR2, C-X-C chemokine receptor type 2; CRC, colorectal cancer; GCN2, general control nonderepressible 2; IGSF9, immunoglobulin superfamily member 9

Back to article page

ISSN: 1475-2867

Contact us

General enquiries: journalsubmissions@springernature.com

Cancer Cell International

Contact us