Targeting MHC-I molecules for cancer: function, mechanism, and therapeutic prospects

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Dec. 2, 2023

Abstract The molecules of Major histocompatibility class I (MHC-I) load peptides and present them on the cell surface, which provided immune system with signal to detect eliminate infected or cancerous cells. In context cancer, owing crucial immune-regulatory roles played by MHC-I molecules, abnormal modulation expression function could be hijacked tumor cells escape surveillance attack, thereby promoting tumoral progression impairing efficacy cancer immunotherapy. Here we reviewed discussed recent studies discoveries related their multidirectional functions in development mainly focusing interactions between multiple participators microenvironment highlighting significance targeting for optimizing immunotherapy a deeper understanding dynamic nature functioning mechanism cancer.

Language: Английский

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A Newly Established Cuproptosis-Associated Long Non-Coding RNA Signature for Predicting Prognosis and Indicating Immune Microenvironment Features in Soft Tissue Sarcoma

Journal of Oncology, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 27

Published: July 6, 2022

Cuproptosis, a new type of programmed cell death, is involved in the development and progression malignancies. The study cuproptosis-associated long non-coding RNAs (lncRNAs) soft tissue sarcomas (STSs) however limited. There also uncertainty regarding prognostic accuracy lncRNAs STSs their relationship to tumor immune microenvironment. aim this was determine significance cuprotosis-associated Transcriptomic clinical data from patients with were obtained through Cancer Genome Atlas (TCGA). Overall, 259 randomly allocated training group or testing group. In group, lncRNA signature constructed, verified On basis risk scores features, we later developed hybrid nomogram. We performed functional microenvironment analysis based on signature. A 5 created. Based signature, categorized STS into high-risk low-risk groups. showed that at high had worse prognosis than those low risk. nomogram then constructed combining characteristics scores, it shown have credible predictive power. Functional enrichment microenvironmental analyses tend be immunologically sensitive tumors. our study, found which serves as an independent indicator. Cuproptosis-associated may play role microenvironment, might therapeutic target for STSs.

Language: Английский

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TDO2+ myofibroblasts mediate immune suppression in malignant transformation of squamous cell carcinoma

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(19)

Published: Aug. 16, 2022

Characterization of the dynamic change in immunological landscape during malignant transformation from precancerous lesions to cancerous squamous cell carcinoma (SCC) is critical for application immunotherapy. Here, we performed single-cell RNA-Seq (scRNA-Seq) 131,702 cells 13 tissues oral (OSCC), 3 samples leukoplakia, and 8 adjacent normal samples. We found that tumor-infiltrating CD4+ CD8+ T were functionally inhibited by immunosuppressive ligands expressed on various types myeloid or neutrophils process carcinogenesis. Notably, identified a subset myofibroblasts exclusively tryptophan 2,3-dioxygenase (TDO2). These TDO2+ located distally tumor nests, both enriched around them. Functional experiments revealed more likely possess ability chemotaxis toward but induced into Tregs caused dysfunction. further showed use TDO2 inhibitor LM10 attenuated inhibitory states cells, restored antitumor response, prevented progression OSCC murine models. Our study reveals multistep transcriptomic demonstrates are potential targets

Language: Английский

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Potential Role of CXCL13/CXCR5 Signaling in Immune Checkpoint Inhibitor Treatment in Cancer

Cancers, Journal Year: 2022, Volume and Issue: 14(2), P. 294 - 294

Published: Jan. 7, 2022

Immune checkpoint inhibitors (ICIs), including antibodies that target programmed cell death protein 1 (PD-1), death-ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA4), represent some of the most important breakthroughs in new drug development for oncology therapy from past decade. CXC chemokine ligand 13 (CXCL13) exclusively binds receptor type 5 (CXCR5), which plays a critical role immune recruitment and activation regulation adaptive response. CXCL13 is key molecular determinant formation tertiary lymphoid structures (TLSs), are organized aggregates T, B, dendritic cells participate antitumor may also serve as prognostic predictive factor, played by ICI-responsive tumor types has gained intense interest. This review discusses how CXCL13/CXCR5 signaling modulates cancer to promote infiltration, antigens, differentiation increase We summarize recent preclinical clinical evidence regarding ICI-therapeutic implications targeting axis discuss potential this pathway immunotherapy.

Language: Английский

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SOX2 function in cancers: Association with growth, invasion, stemness and therapy response

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 156, P. 113860 - 113860

Published: Oct. 20, 2022

Language: Английский

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Synergistic induction of tertiary lymphoid structures by chemoimmunotherapy in bladder cancer

British Journal of Cancer, Journal Year: 2024, Volume and Issue: 130(7), P. 1221 - 1231

Published: Feb. 8, 2024

Abstract Background A substantial number of patients with bladder cancer fail to benefit from immune checkpoint inhibitors (ICIs). We aim investigate whether the addition other therapeutic modalities into immunotherapy may augment reactivity, thereby improving overall response rate. Methods conducted a comprehensive assessment immunological changes following and chemotherapy, employing both single-cell RNA sequencing bulk analyses. Results The patient treated ICIs exhibited higher abundance B cells T follicular helper compared treatment-naïve patient. Analysis public datasets in-house RJBLC-I2N003 cohort revealed induction tertiary lymphoid structure (TLS) neogenesis maturation by immunotherapy. IMvigor 210 study suggested that TLS could serve as predictor prognosis. In addition, genome-wide transcriptome data unveiled shift towards immune-enriched subtype over desert in receiving neoadjuvant chemotherapy. Notably, proportions CD20 + cells, TLSs were significantly increased. combination chemotherapy ICIs, positivity maturity improved baseline. Furthermore, chemoimmunotherapy resulted rate pathological complete monotherapies. Conclusions This work pinpointed individual effect fostering development, underscored superior effectiveness combined enhancing rates.

Language: Английский

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Natural products and derivatives in renal, urothelial and testicular cancers: Targeting signaling pathways and therapeutic potential

Phytomedicine, Journal Year: 2024, Volume and Issue: 127, P. 155503 - 155503

Published: Feb. 28, 2024

Language: Английский

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Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 25, 2022

Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the environment of invasive and cancers share common features cell exhaustion through activation checkpoint pathways. This observation gave rise to several preclinical studies clinical case reports describing blockade Programmed Cell Death Protein 1 Cytotoxic T-Lymphocyte Antigen 4 pathways as an adjunct enhancement strategy treat opportunistic infections. The first part this review summarizes emerging for contributions immunopathology sepsis, mold infections, dimorphic We then potential merits inhibitors (ICIs) antifungal immunotherapy, including incomplete knowledge mechanisms involved both immuno-protective effects toxicities. In second review, we discuss limitations current many unknowns about ICIs strategy. Based on these gaps lessons learned from cancer immunology studies, outline a research agenda determine "sweet spot" medical mycology. specifically importance more nuanced animal models, need study ICI-based combination therapy, ICI resistance, role microenvironment, impact given oncological therapies natural immunity various pathogenic fungi.

Language: Английский

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Bioinformatics construction and experimental validation of a cuproptosis-related lncRNA prognostic model in lung adenocarcinoma for immunotherapy response prediction

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Feb. 11, 2023

Abstract Cuproptosis is a newly form of cell death. related lncRNA in lung adenocarcinoma (LUAD) has also not been fully elucidated. In the present study, we aimed to construct prognostic signature based on cuproptosis-related LUAD and investigate its association with immunotherapy response. The RNA-sequencing data, clinical information simple nucleotide variation patients were obtained from TCGA database. LASSO Cox regression was used signature. CIBERSORT, ESTIMATE ssGSEA algorithms applied assess between risk score TME. TIDE reflect efficiency influence overexpression TMPO-AS1 A549 assessed by vitro experiments. included AL606834.1, AL138778.1, AP000302.1, AC007384.1, AL161431.1, KIAA1671-AS1. Low-risk group exhibited much higher immune score, stromal but lower tumor purity compared high-risk groups. Also, low-risk associated cells function sets, indicating an activation state. had relative TMB. External validation using IMvigor210 cohort demonstrated that better prognosis might more easily benefit immunotherapy. Overexpression promoted proliferation, migration invasion line. novel could predict patients, helped clinicians stratify appropriate for determine individual therapeutic strategies.

Language: Английский

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Five latent factors underlie response to immunotherapy

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(10), P. 2112 - 2120

Published: Sept. 12, 2024

Only a subset of patients treated with immune checkpoint inhibitors (CPIs) respond to the treatment, and distinguishing responders from non-responders is major challenge. Many proposed biomarkers CPI response survival probably represent alternative measurements same aspects tumor, its microenvironment or host. Thus, we currently ignore how many truly independent there are. With an unbiased analysis genomics, transcriptomics clinical data cohort metastatic tumors (n = 479), discovered five orthogonal latent factors: tumor mutation burden, T cell effective infiltration, transforming growth factor-beta activity in microenvironment, prior treatment proliferative potential. Their association was observed across all types validated six cohorts 1,491). These factors constitute frame reference organize current future knowledge on survival.

Language: Английский

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