A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients

Li, Chuan; Phoon, Yee Peng; Karlinsey, Keaton; Tian, Ye; Thapaliya, Samjhana; Thongkum, Angkana; Qu, Lili; Matz, Alyssa; Cameron, Mark J.; Cameron, Cheryl M.; Ménoret, Antoine; Funchain, Pauline; Song, Jung‐Min; Díaz-Montero, C. Marcela; Tamilselvan, Banumathi; Golden, Jackelyn B.; Cartwright, Michael; Rodríguez, Annabelle; Bonin, Christopher; Vella, Anthony T.; Zhou, Beiyan; Gastman, Brian

doi:10.1084/jem.20202084

Cited by 47 publications

(62 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, a team has identified in the blood and tumors of melanoma patients a new CD8+ subpopulation with high levels of OXPHOS, strong expression of the ectonucleotidases CD38 and CD39, exhaustion markers and cytotoxicity. A high proportion of this CD8+ subpopulation correlates to immunotherapy resistance [ 98 ] ( Figure 3 ).…”

Section: Lipid Metabolism In Adaptive Immunitymentioning

confidence: 99%

Impact of Lipid Metabolism on Antitumor Immune Response

Mabrouk

Lecoeur

Bettaı̈eb

et al. 2022

Cancers

View full text Add to dashboard Cite

Over the past decade, metabolic reprogramming has been defined as a hallmark of cancer. More recently, a large number of studies have demonstrated that metabolic reprogramming can modulate the differentiation and functions of immune cells, and thus modify the antitumor response. Increasing evidence suggests that modified energy metabolism could be responsible for the failure of antitumor immunity. Indeed, tumor-infiltrating immune cells play a key role in cancer, and metabolic switching in these cells has been shown to help determine their phenotype: tumor suppressive or immune suppressive. Recent studies in the field of immunometabolism focus on metabolic reprogramming in the tumor microenvironment (TME) by targeting innate and adaptive immune cells and their associated anti- or protumor phenotypes. In this review, we discuss the lipid metabolism of immune cells in the TME as well as the effects of lipids; finally, we expose the link between therapies and lipid metabolism.

show abstract

Section: Lipid Metabolism In Adaptive Immunitymentioning

confidence: 99%

Impact of Lipid Metabolism on Antitumor Immune Response

Mabrouk

Lecoeur

Bettaı̈eb

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…Additionally, singlecell transcriptomics was utilized to predict the therapy response in melanoma patients. A CD8 + T cell subpopulation with high levels of oxidative phosphorylation was identified that distinguished immune checkpoint inhibitor responders from non-responders [65]. Similar approaches could be translated to neurology, supporting clinicians in challenging decisions.…”

Section: Disease Monitoring and Clinical Management Of Patients Based...mentioning

confidence: 91%

High-dimensional investigation of the cerebrospinal fluid to explore and monitor CNS immune responses

et al. 2022

View full text Add to dashboard Cite

The cerebrospinal fluid (CSF) features a unique immune cell composition and is in constant contact with the brain borders, thus permitting insights into the brain to diagnose and monitor diseases. Recently, the meninges, which are filled with CSF, were identified as a neuroimmunological interface, highlighting the potential of exploring central nervous system (CNS) immunity by studying CNS border compartments. Here, we summarize how single-cell transcriptomics of such border compartments advance our understanding of neurological diseases, the challenges that remain, and what opportunities novel multi-omic methods offer. Single-cell transcriptomics studies have detected cytotoxic CD4+ T cells and clonally expanded T and B cells in the CSF in the autoimmune disease multiple sclerosis; clonally expanded pathogenic CD8+ T cells were found in the CSF and in the brain adjacent to β-amyloid plaques of dementia patients; in patients with brain metastases, CD8+ T cell clonotypes were shared between the brain parenchyma and the CSF and persisted after therapy. We also outline how novel multi-omic approaches permit the simultaneous measurements of gene expression, chromatin accessibility, and protein in the same cells, which remain to be explored in the CSF. This calls for multicenter initiatives to create single-cell atlases, posing challenges in integrating patients and modalities across centers. While high-dimensional analyses of CSF cells are challenging, they hold potential for personalized medicine by better resolving heterogeneous diseases and stratifying patients.

show abstract

“…Nevertheless, another study has identified a unique CD8 + T-cell blood/tumor-shared subpopulation in melanoma patients with high levels of oxidative phosphorylation, which is correlated with immune checkpoint inhibitor (ICI) resistance in melanoma patients. The establishment of a transcriptomic profile reflecting CD8 + T cells with high oxidative phosphorylation can be effective in discerning responders from non-responders ( 105 ). The above two studies seem to display contrary conclusions, which might be due to distinct cellular sources of mitochondria in the TME.…”

Section: Mitochondrial Oxidative Phosphorylation In Melanoma Immunologymentioning

confidence: 99%

Metabolic rewiring directs melanoma immunology

et al. 2022

View full text Add to dashboard Cite

Melanoma results from the malignant transformation of melanocytes and accounts for the most lethal type of skin cancers. In the pathogenesis of melanoma, disordered metabolism is a hallmark characteristic with multiple metabolic paradigms involved in, e.g., glycolysis, lipid metabolism, amino acid metabolism, oxidative phosphorylation, and autophagy. Under the driving forces of oncogenic mutations, melanoma metabolism is rewired to provide not only building bricks for macromolecule synthesis and sufficient energy for rapid proliferation and metastasis but also various metabolic intermediates for signal pathway transduction. Of note, metabolic alterations in tumor orchestrate tumor immunology by affecting the functions of surrounding immune cells, thereby interfering with their antitumor capacity, in addition to the direct influence on tumor cell intrinsic biological activities. In this review, we first introduced the epidemiology, clinical characteristics, and treatment proceedings of melanoma. Then, the components of the tumor microenvironment, especially different populations of immune cells and their roles in antitumor immunity, were reviewed. Sequentially, how metabolic rewiring contributes to tumor cell malignant behaviors in melanoma pathogenesis was discussed. Following this, the proceedings of metabolism- and metabolic intermediate-regulated tumor immunology were comprehensively dissertated. Finally, we summarized currently available drugs that can be employed to target metabolism to intervene tumor immunology and modulate immunotherapy.

show abstract

A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients

Cited by 47 publications

References 96 publications

Impact of Lipid Metabolism on Antitumor Immune Response

Impact of Lipid Metabolism on Antitumor Immune Response

High-dimensional investigation of the cerebrospinal fluid to explore and monitor CNS immune responses

Metabolic rewiring directs melanoma immunology

Contact Info

Product

Resources

About