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Series GSE260816 Query DataSets for GSE260816
Status Public on Mar 04, 2024
Title Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone. However, there remains little consensus on the mechanism(s) of response with this combination. Here we find that a high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients treated with atezolizumab plus tiragolumab but not with atezolizumab alone. Serum sample analysis revealed that macrophage activation is associated with a clinical benefit in patients who received the combination treatment. In mouse tumour models, tiragolumab surrogate antibodies inflamed tumour-associated macrophages, monocytes and dendritic cells through Fcγ receptors (FcγR), in turn driving anti-tumour CD8+ T cells from an exhausted effector-like state to a more memory-like state. These results reveal a mechanism of action through which TIGIT checkpoint inhibitors can remodel immunosuppressive tumour microenvironments, and suggest that FcγR engagement is an important consideration in anti-TIGIT antibody development.
 
Overall design The CT26 mouse colon carcinoma cell line was obtained from American Type Culture Collection. A total of 100,000 CT26 cells was inoculated subcutaneously into the right unilateral flank of the syngeneic BALB/c mice. All mice used were 6-8 week old and female. After approximately 10–12 days, mice bearing tumours of 150–200 mm3 were randomized into treatment groups on the basis of tumour size and treated with anti-mouse PD-L1 (6E11, isotype IgG2a LALAPG, 10 mg per kg), anti-mouse TIGIT (10A7, isotypes IgG2a, mIgG2b, and IgG2a LALAPG, 10 mg per kg), anti-mouse CSF-1R (Bioexcell, BP0213, 30 mg per kg) and/or anti-gp120 control antibodies (IgG2a isotype, to total 35 mg per kg overall antibody dosing). Antibodies were administered once intravenously, and 72 h after treatment, mice were euthanized by asphyxiation and CD45+ cells were collected for scRNA-seq analysis.
Web link https://www.nature.com/articles/s41586-024-07121-9
 
Contributor(s) Guan X, Hu R, Choi Y, Srivats S, Nabet BY, Silva J, McGinnis L, Hendricks R, Nutsch K, Banta KL, Duong E, Dunkle A, Chang PS, Han C, Mittman S, Molden N, Daggumati P, Connolly W, Johnson M, Abreu D, Cho B, Italiano A, Gil-Bazo I, Felip E, Mellman I, Mariathasan S, Shames DS, Meng R, Chiang EY, Johnston RJ, Patil NS
Citation(s) 38418879, 39164390
BioProject PRJNA1082777
Submission date Mar 04, 2024
Last update date Oct 09, 2024
Contact name Xiangnan Guan
E-mail(s) guanx8@gene.com
Organization name Genentech
Street address 1 DNA WAY
City South San Francisco
State/province California
ZIP/Postal code 94080
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (46)
GSM8124966 blood_ctrl_ADT_EXP_anti_TIGIT_monoTx_batch1
GSM8124967 blood_ctrl_mRNA_EXP_anti_TIGIT_monoTx_batch1
GSM8124968 blood_tigitlalapg_ADT_EXP_anti_TIGIT_monoTx_batch1

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE260816_feature_reference.csv.gz 207 b (ftp)(http) CSV
GSE260816_mouse_scSeq_anti-CSF1R_tumor_T_NK_RNA_raw_counts.rds.gz 112.7 Mb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-CSF1R_tumor_T_NK_metadata.rds.gz 745.8 Kb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-CSF1R_tumor_myeloid_RNA_raw_counts.rds.gz 16.9 Mb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-CSF1R_tumor_myeloid_metadata.rds.gz 141.4 Kb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_comboTx_blood_RNA_raw_counts.rds.gz 232.9 Mb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_comboTx_blood_metadata.rds.gz 2.1 Mb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_comboTx_tumor_T_NK_RNA_raw_counts.rds.gz 199.6 Mb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_comboTx_tumor_T_NK_metadata.rds.gz 1.4 Mb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_comboTx_tumor_myeloid_RNA_raw_counts.rds.gz 18.0 Mb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_comboTx_tumor_myeloid_metadata.rds.gz 185.5 Kb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_monoTx_blood_RNA_raw_counts.rds.gz 93.9 Mb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_monoTx_blood_metadata.rds.gz 879.4 Kb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_monoTx_tumor_T_NK_RNA_raw_counts.rds.gz 112.2 Mb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_monoTx_tumor_T_NK_metadata.rds.gz 863.6 Kb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_monoTx_tumor_myeloid_RNA_raw_counts.rds.gz 28.6 Mb (ftp)(http) RDS
GSE260816_mouse_scSeq_anti-TIGIT_monoTx_tumor_myeloid_metadata.rds.gz 231.9 Kb (ftp)(http) RDS
GSE260816_readme.txt 610 b (ftp)(http) TXT
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