Unravelling Tumour Microenvironment in Melanoma at Single-Cell Level and Challenges to Checkpoint Immunotherapy
Abstract
:1. The Emergence of Single-Cell Sequencing and Spatial Platforms to Dissect Melanoma Microenvironment
1.1. Single-Cell Sequencing
1.2. Spatially Resolved Genomics and Transcriptomics
2. Insights into Heterogeneity of Tumour Microenvironment from Single-Cell Expression Profiling
2.1. Inter- and Intra-Tumoural Heterogeneity
2.2. The Spectrum of Spatial and Temporal Intra-Tumoural Heterogeneity
3. Clinical Considerations of Tumour Microenvironment Heterogeneity in Response and Resistance to Checkpoint-Based Immunotherapies
3.1. Impact of Tumour and Immune Microenvironment Heterogeneity on Response to Immunotherapies
3.2. Heterogenous Responses in Patients with Innate and Acquired Resistance
4. Heterogenous Expression of PD-L1 in the Tumour-Immune Microenvironment
5. Integrating Tumour Microenvironment Heterogeneity into Clinical Decision Making
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Target | Drug | Clinical Trial ID | Phase | Settings | Tumour Types | Treatment Arms | Status |
---|---|---|---|---|---|---|---|
LAG-3 | Eftilagimod α (IMP321) | NCT03252938 | 1 | Advanced/metastatic | Solid tumours | Eftilagimod α | Recruiting |
NCT00324623 | 1 | Advanced/metastatic | Melanoma | Cyclophosphamide, fludarabine followed by melan-A VLP vaccine and eftilagimod α | Completed | ||
NCT00365937 | 1 | Adjuvant | Melanoma | Eftilagimod α ± HLA-A2 peptides | Terminated | ||
NCT01308294 | 1, 2 | Stage II-1V | Melanoma | Eftilagimod α + tumour antigenic peptides + monatide | Terminated | ||
Relatlimab (BMS-986016) | NCT02966548 | 1 | Advanced/metastatic | Solid tumours | Relatlimab ± nivolumab | Active, not recruiting | |
NCT01968109 | 1 | First. second line | Solid tumours | Relatlimab ± nivolumab | Active, not recruiting | ||
NCT03743766 | 2 | Advanced/metastatic | Melanoma | Relatlimab + nivolumab | Recruiting | ||
NCT03470922 | 2, 3 | Advanced/metastatiC | Melanoma | Relatlirnab ± nivolumab | Active, not recruiting | ||
NCT03335540 | 1, 2 | Advanced/metastatic | Sold tumours | Relatlimab + nivolumab or cabiralizumab or ipilimumab or IDO1 inhibitor or radiation therapy | Active, not recruiting | ||
NCT02519322 | 2 | Neoadjuvant and adjuvant | Melanoma | Nivolumab ± relatlimab or ipilimumab | Recruiting | ||
NCT03459222 | 2 | Advanced/metastatic | Solid tumours | Relatlimab + nivolumab + IDO1 inhibitor or relatlimab + nivolumab + ipilimumab | Recruiting | ||
LAG525 | NCT02460224 | 1, 2 | Advanced/metastatic | Solid tumours | LAG525 ± spartalizumab (anti-PD-1) | Completed | |
NCT03365791 | 2 | Advanced/metastatic | Solid or hematologic malignancy | LAG525 + spartalizumab (anti-PD-1) | Completed | ||
Fianlimab (REGN3767) | NCT03005782 | 1 | Advanced/metastatic | Solid tumours or lymphomas | Fianlimab ± cemiplimab (anti-PD-1) | Active, not recruiting | |
BI 754111 | NCT03433898 | 1 | Advanced/metastatic | Solid tumours | BI 754111 ± BI 754091 (anti-PD-1) | Active, not recruiting | |
NCT03156114 | 1 | Advanced/metastatic | Solid tumours | BI 754111 ± BI 754091 (anti-PD-1) | Active, not recruiting | ||
NCT03697304 | 2 | Advanced/metastatic | Solid tumours | BI 754111 or BI 836880 (bispecific VEGF and Ang2 Ab) + BI 754091 (anti-PD-1) | Active, not recruiting | ||
NCT03964233 | 1 | Advanced/metastatic | Solid tumours | BI 754111 + BI 754091 ± BI 907828 (MDM2-p53 antagonist) | Recruiting | ||
Sym022 | NCT03489369 | 1 | Advanced/metastatic | Solid tumours or lymphomas | Sym022 | Completed | |
NCT03311412 | 1 | Advanced/metastatic | Solid tumours or lymphomas | Sym022 + Sym021 (anti-PD-1) ± Sym023 (anti-TIM-3) | Completed | ||
MGD013 | NCT03219268 | 1 | Advanced/metastatic | Solid or hematologic malignancy | MGD013 + margetuximab (anti-HER2 monoclonal antibody) | Active, not recruiting | |
TSR-033 | NCT03250832 | 1 | Advanced/metastatic | Solid tumours | TSR-033 ± dostarlimab ± mFOLFOX6 or FOLFIRI ± bevacizumab | Active, not recruiting | |
INCAGN02385 | NCT03538028 | 1 | Advanced/metastatic | Solid tumours | INCAGN02385 | Completed | |
NCT04370704 | 1, 2 | Advanced/metastatic | Solid tumours | INCAGN02385 + INCAGN02390 (Anti-TIM-3) ± INCMGA00012 (anti-PD-1) | Recruiting | ||
XmAb22841 | NCT03849469 | 1 | Advanced/metastatic | Solid tumours | XmAb22841 ± pembrolizumab | Active, not recruiting | |
LBL-007 | NCT04640545 | 1 | Advanced/metastatic | Melanoma | LBL-007 + toriparimab (anti-PD-1) | Recruiting | |
FS118 | NCT03440437 | 1 | Advanced/metastatic | Solid or hematologic malignancy | FS118 | Recruiting | |
RO7247669 | NCT04140500 | 1 | Advanced/metastatic | Solid tumours | RO7247669 | Recruiting | |
EMB-02 | NCT04618393 | 1, 2 | Advanced/metastatic | Solid tumours | EMB-02 | Recruiting | |
TIGIT | Tiragolumab (MTIG7192A/RG-6058) | NCT02794571 | 1 | Locally advanced or metastatic | Solid tumours | Tiragolumab ± atezolizumab ± chemotherapy | Recruiting |
Vibostolimab (MK-7684) | NCT02964013 | 1 | Advanced/metastatic | Solid tumours | Vibostolimab ± pembrolizumab ± pemetrexed/carboplatin: carboplatin + cisplatin + etoposide | Active, not recruiting | |
NCT04305054 | 1, 2 | First line | Melanoma | Pembrolizumab ± vibostolimab or quavonlimab (MK-1308) ± lenvatinib | Recruiting | ||
NCT04305041 | 1, 2 | Stage IV | Melanoma | Pembrolizumab ± guavonlimab + vibostolimab or lenvatinib | Recruiting | ||
NCT04303169 | 1, 2 | Stage III | Melanoma | Pembrolizumab ± vibostolimab or V937 (oncolytic virus) | Recruiting | ||
OMP-313M32 | NCT03119428 | 1 | Locally advanced or metastatic | Solid tumours | OMP-313M32 ± nivolumab | Terminated | |
BMS-986207 | NCT02913313 | 1, 2 | Advanced/metastatic | Solid tumours | BMS-986207 ± nivolumab ± ipilimumab | Recruiting | |
NCT04570839 | 1, 2 | Advanced/metastatic | Solid tumours | BMS-986207 + nivolumab + COM701 (anti-PVRIG Ab) | Recruiting | ||
Domvanalimab (AB-154) | NCT03628677 | 1 | Advanced/metastatic | Solid tumours | Dombvanalimab + zimberelimab (AB122, anti-PD-1) | Active, not recruiting | |
ASP8374 | NCT03945253 | 1 | Advanced/metastatic | Solid tumours | ASP8374 | Completed | |
NCT03260322 | 1 | Advanced/metastatic | Solid tumours | ASP8374 ± pembrolizumab | Completed | ||
IBI939 | NCT04353830 | 1 | Advanced/metastatic | Solid tumours | IBI939 ± sintilimab (anti-PD-1) | Recruiting | |
Ociperlimab (BGB-A1217) | NCT04047862 | 1 | Advanced/metastatic | Solid tumours | Ociperlimab + tislelizumab (anti-PD-1) ± chemotherapy | Recruiting | |
COM902 | NCT04354246 | 1 | Advanced/metastatic | Solid tumours | COM902 ± COM701 (anti-PVRIG Ab) | Recruiting | |
M6223 | NCT04457778 | 1 | Advanced/metastatic | Solid tumours | M6223 ± bintrafusp alfa (M7824, bispecific TGF-β and PD-L1 Ab) | Recruiting | |
TIM-3 | Sym023 | NCT03489343 | 1 | Advanced/metastatic | Solid tumours or lymphomas | Sym023 | Completed |
LY3321367 | NCT03099109 | 1 | Advanced/metastatic | Solid tumours | LY3300054 (anti-PD-L1) + LY3321367 | Active, not recruiting | |
NCT02791334 | 1 | Advanced/metastatic | Solid tumours | LY3300054 (anti-PD-L1) ± LY3321367 or abemaciclib or ramucirumab or merestinib | Active, not recruiting | ||
Cobolimab (TSR-022) | NCT02817633 | 1 | Advanced/metastatic | Solid tumours | Cobolimab ± nivolumab or TSR-042 (anti-PD-1) ± TSR-033 or chemotherapy | Recruiting | |
NCT03307785 | 1 | Advanced/metastatic | Solid tumours | Dostarlimab (TSR-042, anti-PD-1) ± TSR-022 + chemotherapy | Active, not recruiting | ||
NCT04139902 | 2 | Ncoadjuvant | Melanoma | Cobolimab ± dostarlimab (TSR-042, anti-PD-1) | Recruiting | ||
Sabatolimab (MBG453) | NCT02608268 | 1, 2 | Advanced/metastatic | Solid tumours | Sabatolimab ± PDR001 vs. chemotherapy | Active, not recruiting | |
INCAGN02390 | NCT03652077 | 1 | Advanced/metastatic | Solid tumours | INCAGN02390 | Completed | |
BMS-986258 | NCT03446040 | 1, 2 | Advanced/metastatic | Solid tumours | BMS-986258 + nivolumab or rHuPH20 | Active, not recruiting | |
SHR-1702 | NCT03871855 | 1 | Advanced/metastatic | Solid tumours | SHR-1702 ± camrelizumab (anti-PD-1) | Unknown | |
RO7121661 | NCT03708328 | 1 | Advanced/metastatic | Solid tumours | RO7121661 | Active, not recruiting | |
B7-H3 | Enoblituzumab (MGA271) | NCT01391143 | 1 | Advanced/metastatic | Solid tumours | Enoblituzumab (MGA271) | Completed |
NCT02381314 | 1 | Advanced/metastatic | Solid tumours | Enoblituzumab + ipilimumab | Completed | ||
NCT02475213 | 1 | Advanced/metastatic | Solid tumours | Enoblituzumab + pembrolizumab or retifanlimab (MGA012, anti-PD-1) | Completed | ||
DS-7300a | NCT04145622 | 1, 2 | Advanced/metastatic | Solid tumours | DS-7300a | Recruiting | |
Orlotamab (MGD009) | NCT02628535 | 1 | Advanced/metastatic | solid tumours | Orlotamab (MGD009) | Terminated | |
NCT03406949 | 1 | Advanced/metastatic | Solid tumours | Orlotamab + retifanlimab (MGA012, anti-PD-1) | Completed | ||
4SCAR-276 | NCT04432649 | 1 | Advanced/metastatic | Solid tumours | 4SCAR-276 | Recruiting | |
VISTA | JNJ-61610588 | NCT02671955 | 1 | Advanced/metastatic | Solid tumours | JNJ-61610588 | Terminated |
CI-8993 | NCT04475523 | 1 | Advanced/metastatic | Solid tumours | CI-8993 | Recruiting | |
CA-170 | NCT02812875 | 1 | Advanced/metastatic | Solid tumours or lymphomas | CA-170 | Completed | |
ICOS | Feladilimab | NCT03693612 | 2 | Advanced/metastatic | Solid tumours | Feladilimab + tremelimumab (anti-CTLA-4) vs. chemotherapy | Completed |
JTX-2011 | NCT02904226 | 1, 2 | Advanced/metastatic | Solid tumours | JTX-2011 ± pembrolizumab or nivolumab or ipilimumab | Completed | |
KY1044 | NCT03829501 | 1, 2 | Advanced/metastatic | Solid tumours | KY1044 ± atezolizumab | Recruiting | |
BTLA | INBRX-106 | NCT04198766 | 1 | Locally advanced or metastatic | Solid tumours | INBRX-106 ± pembrolizumab | Recruiting |
Cudarolimab (IBI101) | NCT03758001 | 1 | Advanced/metastatic | Solid tumours | Cudarcenab ± sintilimab (anti-PD-1) | Active, not recruiting | |
PF-04518600 | NCT02315066 | 1 | Advanced/metastatic | Solid tumours | PF-04518600 ± utomilumab (PF-05082566, agonist anti-TNFRSF9 Ab) | Completed | |
TAB004 (JS004) | NCT04137900 | 1 | Advanced/metastatic | Solid tumours or lymphomas | TAB004 ± toripalimab (anti-PD-1) | Recruiting | |
NCT04278859 | 1 | Advanced/metastatic | Solid tumours | TAB004 (JS004) | Unknown |
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Bai, X.; Quek, C. Unravelling Tumour Microenvironment in Melanoma at Single-Cell Level and Challenges to Checkpoint Immunotherapy. Genes 2022, 13, 1757. https://doi.org/10.3390/genes13101757
Bai X, Quek C. Unravelling Tumour Microenvironment in Melanoma at Single-Cell Level and Challenges to Checkpoint Immunotherapy. Genes. 2022; 13(10):1757. https://doi.org/10.3390/genes13101757
Chicago/Turabian StyleBai, Xinyu, and Camelia Quek. 2022. "Unravelling Tumour Microenvironment in Melanoma at Single-Cell Level and Challenges to Checkpoint Immunotherapy" Genes 13, no. 10: 1757. https://doi.org/10.3390/genes13101757
APA StyleBai, X., & Quek, C. (2022). Unravelling Tumour Microenvironment in Melanoma at Single-Cell Level and Challenges to Checkpoint Immunotherapy. Genes, 13(10), 1757. https://doi.org/10.3390/genes13101757