RAS signaling and immune cells: a sinister crosstalk in the tumor microenvironment

Liu, Yongting; Xie, Bin; Chen, Qiong

doi:10.1186/s12967-023-04486-9

Cited by 3 publications

(1 citation statement)

References 136 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This pathway also plays a role in the regulation of PD-L1 163 . Similarly, tumor cells defective in the RAS/KRAS pathway interact with immune cells in the TME by secreting a series of cytokines, such as TGF-β, IL-8, and IL-6, which are involved in macrophage reprogramming and the regulation of Treg differentiation 166 . However, the participation of these pathways in NF2 -associated tumors has not been extensively characterized.…”

Section: Nf2 and Immunotherapymentioning

confidence: 99%

NF2: An underestimated player in cancer metabolic reprogramming and tumor immunity

Xu,

Yin,

Shu

2024

npj Precis. Onc.

View full text Add to dashboard Cite

Neurofibromatosis type 2 (NF2) is a tumor suppressor gene implicated in various tumors, including mesothelioma, schwannomas, and meningioma. As a member of the ezrin, radixin, and moesin (ERM) family of proteins, merlin, which is encoded by NF2, regulates diverse cellular events and signalling pathways, such as the Hippo, mTOR, RAS, and cGAS-STING pathways. However, the biological role of NF2 in tumorigenesis has not been fully elucidated. Furthermore, cross-cancer mutations may exert distinct biological effects on tumorigenesis and treatment response. In addition to the functional inactivation of NF2, the codeficiency of other genes, such as cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B), BRCA1-associated protein-1 (BAP1), and large tumor suppressor 2 (LATS2), results in unique tumor characteristics that should be considered in clinical treatment decisions. Notably, several recent studies have explored the metabolic and immunological features associated with NF2, offering potential insights into tumor biology and the development of innovative therapeutic strategies. In this review, we consolidate the current knowledge on NF2 and examine the potential connection between cancer metabolism and tumor immunity in merlin-deficient malignancies. This review may provide a deeper understanding of the biological roles of NF2 and guide possible therapeutic avenues.

show abstract

Section: Nf2 and Immunotherapymentioning

confidence: 99%

NF2: An underestimated player in cancer metabolic reprogramming and tumor immunity

Xu,

Yin,

Shu

2024

npj Precis. Onc.

View full text Add to dashboard Cite

show abstract

MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer

Casacuberta-Serra,

González-Larreategui,

Capitán-Leo

et al. 2024

Sig Transduct Target Ther

View full text Add to dashboard Cite

RAS and MYC rank amongst the most commonly altered oncogenes in cancer, with RAS being the most frequently mutated and MYC the most amplified. The cooperative interplay between RAS and MYC constitutes a complex and multifaceted phenomenon, profoundly influencing tumor development. Together and individually, these two oncogenes regulate most, if not all, hallmarks of cancer, including cell death escape, replicative immortality, tumor-associated angiogenesis, cell invasion and metastasis, metabolic adaptation, and immune evasion. Due to their frequent alteration and role in tumorigenesis, MYC and RAS emerge as highly appealing targets in cancer therapy. However, due to their complex nature, both oncogenes have been long considered “undruggable” and, until recently, no drugs directly targeting them had reached the clinic. This review aims to shed light on their complex partnership, with special attention to their active collaboration in fostering an immunosuppressive milieu and driving immunotherapeutic resistance in cancer. Within this review, we also present an update on the different inhibitors targeting RAS and MYC currently undergoing clinical trials, along with their clinical outcomes and the different combination strategies being explored to overcome drug resistance. This recent clinical development suggests a paradigm shift in the long-standing belief of RAS and MYC “undruggability”, hinting at a new era in their therapeutic targeting.

show abstract

Sex disparities revealed by single-cell and bulk sequencing and their impacts on the efficacy of immunotherapy in esophageal cancer

Yan,

Huang,

et al. 2024

Biol Sex Differ

View full text Add to dashboard Cite

Background There is an ongoing debate on whether sex affects immune-suppressive tumor microenvironment and immunotherapy. Here, we explored the underlying molecular bases for sex dimorphisms and their impact on the efficacy of immunotherapy in esophageal cancer (EC). Methods 2360 EC patients from phase 3 trials were pooled to compare overall survivals by calculating hazard ratios (HRs) and their 95% confidence intervals (CIs). Genomic data of 1425 samples were integrated to depict the genomic landscapes and antigenic features. We also examined the sex disparities based on single-cell RNA sequencing and T cell receptor-sequencing data from 105,145 immune cells in 60 patients. Results Immunotherapy was associated with favorable outcomes in men (HR, 0.71; 95% CI, 0.65–0.79; P < 0.001), but not in women (HR, 0.98; 95% CI, 0.78–1.23; P = 0.84) (Pinteraction =0.02). The frequencies of 8 gene mutations, 12 single base substitutions signatures, and 131 reactome pathways were significantly different between male and female. Additionally, six subtypes of HLA-II antigens were enriched in women. Hence, we constructed and then validated a sex-related signature to better predict the outcomes of immunotherapy. Exhausted CD8+ T cells were highly infiltrated in men, while naïve CD8+ T cells were more common in women. Further examinations on multiple malignancies suggested exhausted CD8+ T cells were enriched in patients who responded to immunotherapy. Conclusions Our study delineated the robust genomic and cellular sex disparities in EC. Furthermore, male, rather than female, derived significantly benefits from immunotherapy. These results have implications for treatment decision-making and developing immunotherapy for personalized care. Plain English Summary In the past several years, immunotherapy has gradually replaced the traditional chemotherapy as the standard treatment in esophageal cancer. It is well-established that immunological responses in male and female differ significantly. However, there is an ongoing debate on whether sex can impact the treatment outcomes in immunotherapy. In the present study, we systematically characterized the genomic and cellular landscapes of esophageal cancer, and revealed the significant differences between male and female patients. Furthermore, with over 2000 patients with esophageal cancer, we showed that only men can benefit from immunotherapy. In women, immunotherapy failed to show superior over chemotherapy. These results have implications for treatment decision-making and developing next-generation immunotherapy for personalized care.

show abstract

RAS signaling and immune cells: a sinister crosstalk in the tumor microenvironment

Cited by 3 publications

References 136 publications

NF2: An underestimated player in cancer metabolic reprogramming and tumor immunity

NF2: An underestimated player in cancer metabolic reprogramming and tumor immunity

MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer

Sex disparities revealed by single-cell and bulk sequencing and their impacts on the efficacy of immunotherapy in esophageal cancer

Contact Info

Product

Resources

About