Emerging role of autophagy in anti-tumor immunity: Implications for the modulation of immunotherapy resistance

Jiang, Ting; Chen, Xisha; Ren, Xingcong; Yang, Jin‐Ming; Cheng, Yan

doi:10.1016/j.drup.2021.100752

Cited by 41 publications

(27 citation statements)

References 205 publications

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“…Apart from TMB in tumors, the immunosuppressive microenvironment around the tumor may also affect the efficacy of ICIs ( 31 ). Autophagy has been suggested to promote growth of tumors with high TMB by limiting T cell immune responses ( 32 ), and autophagy inhibition can enhance antitumor immunity ( 33 ). Since the mTOR pathway was more likely to be activated (autophagy inhibition) in dA-AL-I-detected samples, whether dA-AL-I detection precisely predicts a better response to ICIs for UTUC with high TMB requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

High Level of Aristolochic Acid Detected With a Unique Genomic Landscape Predicts Early UTUC Onset After Renal Transplantation in Taiwan

Lai

Kong

et al. 2022

Front. Oncol.

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BackgroundThe unusual high dialysis prevalence and upper urinary tract urothelial carcinoma (UTUC) incidence in Taiwan may attribute to aristolochic acid (AA), which is nephrotoxic and carcinogenic, exposure. AA can cause a unique mutagenic pattern showing A:T to T:A transversions (mutational Signature 22) analyzed by whole exome sequencing (WES). However, a fast and cost-effective tool is still lacking for clinical practice. To address this issue, we developed an efficient and quantitative platform for the quantitation of AA and tried to link AA detection with clinical outcomes and decipher the genomic landscape of UTUC in Taiwan.Patients and MethodsWe recruited 61 patients with de novo onset of UTUC after kidney transplantation who underwent radical nephroureterectomy. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) platform was developed for the quantitation of AA. Pearson’s chi-square test, Kaplan–Meier method, and Cox proportional hazard model were utilized to assess the correlations among AA detection, clinicopathological characteristics, and clinical outcomes. Seven tumors and seven paired normal tissues were sequenced using WES (approximately 800x sequencing depth) and analyzed by bioinformatic tool.ResultsWe found that high level of 7-(deoxyadenosin-N6-yl)aristolactam I (dA-AL-I) detected in paired normal tissues was significantly correlated with fast UTUC initiation times after renal transplantation (p = 0.035) and with no use of sirolimus (p = 0.046). Using WES analysis, we further observed that all tumor samples were featured by Signature 22 mutations, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC)-associated gene mutations, p53 mutations, no fibroblast growth factor receptor 3 (FGFR3) mutation, and high tumor mutation burden (TMB). Especially, mammalian target of rapamycin (mTOR) activation predominated in dA-AL-I-detected samples compared with those without dA-AL-I detection and might be associated with UTUC initiation through cell proliferation and suppression of UTUC progression via autophagy inhibition.ConclusionAccordingly, dA-AL-I detection can provide more direct evidence to AA exposure and serve as a more specific predictive and prognostic biomarker for patients with de novo onset of UTUC after kidney transplantation.

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Section: Discussionmentioning

confidence: 99%

High Level of Aristolochic Acid Detected With a Unique Genomic Landscape Predicts Early UTUC Onset After Renal Transplantation in Taiwan

Lai

Kong

et al. 2022

Front. Oncol.

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“…It is widely accepted that the human body, against a tumor, produces an innate immune response, in which immune cells (such as natural killer, NK, macrophages, and T cells) and immune effector molecules (such as CD8+ and CD4+) are the main effectors [ 208 ]. Improving the immune function of these elements with specific immunotherapeutic agents has shown great efficacy against cancer.…”

Section: Autophagy and Tumor Immune Responsementioning

confidence: 99%

“…Similarly, autophagy is fundamental for B cells since a lack of autophagy attenuates the secondary immune response, antigen presenting and processing, and the differentiation of plasma cells [ 220 ]. Finally, autophagy controls the functions of dendritic cells, the activity of myeloid derived suppressor cells (MDSCs), and regulates the formation, maintenance, recruitment, and polarization of macrophages [ 208 ]. Considering all these findings, it is not surprising that autophagy can impact cancer immunotherapy.…”

Section: Autophagy and Tumor Immune Responsementioning

confidence: 99%

Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers

Patergnani

Missiroli

Morciano

et al. 2021

Cancers

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The malignant transformation of a cell produces the accumulation of several cellular adaptions. These changes determine variations in biological processes that are necessary for a cancerous cell to survive during stressful conditions. Autophagy is the main nutrient recycling and metabolic adaptor mechanism in eukaryotic cells, represents a continuous source of energy and biomolecules, and is fundamental to preserve the correct cellular homeostasis during unfavorable conditions. In recent decades, several findings demonstrate a close relationship between autophagy, malignant transformation, and cancer progression. The evidence suggests that autophagy in the cancer context has a bipolar role (it may act as a tumor suppressor and as a mechanism of cell survival for established tumors) and demonstrates that the targeting of autophagy may represent novel therapeutic opportunities. Accordingly, the modulation of autophagy has important clinical benefits in patients affected by diverse cancer types. Currently, about 30 clinical trials are actively investigating the efficacy of autophagy modulators to enhance the efficacy of cytotoxic chemotherapy treatments. A deeper understanding of the molecular pathways regulating autophagy in the cancer context will provide new ways to target autophagy for improving the therapeutic benefits. Herein, we describe how autophagy participates during malignant transformation and cancer progression, and we report the ultimate efforts to translate this knowledge into specific therapeutic approaches to treat and cure human cancers.

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“…As a crucial part of the recycling process in complicated tumor immune microenvironment (TIME), autophagy in tumor immunity has been increasingly appreciated ( Li et al, 2015 ). For example, Jiang et al illustrated the impact of autophagy on TIME from three perspectives and proposed that autophagy-based therapy combined with immunotherapy may be promising ( Jiang et al, 2021 ). Gerada and Ryan (2020) explained that TIME determines whether autophagy promotes or inhibits tumors.…”

Section: Introductionmentioning

confidence: 99%

Identification of an Autophagy-Related lncRNA Prognostic Signature and Related Tumor Immunity Research in Lung Adenocarcinoma

Chen

Sang

et al. 2021

Front. Genet.

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Autophagy is closely associated with the tumor immune microenvironment (TIME) and prognosis of patients with lung adenocarcinoma (LUAD). In the present study, we established a signature on the basis of long noncoding RNAs (lncRNAs) related to autophagy (ARlncRNAs) to investigate the TIME and survival of patients with LUAD. We selected ARlncRNAs associated with prognosis to construct a model and divided each sample into different groups on the basis of risk score. The ARlncRNA signature could be recognized as an independent prognostic factor for patients with LUAD, and patients in the low-risk group had a greater survival advantage. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis suggested that several immune functions and pathways were enriched in different groups. A high-risk score correlated significantly negatively with high abundance of immune cells and stromal cells around the tumor and high tumor mutational burden. Low-risk patients had a higher PD-1, CTLA-4, and HAVCR2 expression and had a better efficacy of immune checkpoint inhibitors, including PD-1/CTLA-4 inhibitor. A reliable signature on the basis of ARlncRNAs was constructed to explore the TIME and prognosis of patients with LUAD, which could provide valuable information for individualized LUAD treatment.

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Emerging role of autophagy in anti-tumor immunity: Implications for the modulation of immunotherapy resistance

Cited by 41 publications

References 205 publications

High Level of Aristolochic Acid Detected With a Unique Genomic Landscape Predicts Early UTUC Onset After Renal Transplantation in Taiwan

High Level of Aristolochic Acid Detected With a Unique Genomic Landscape Predicts Early UTUC Onset After Renal Transplantation in Taiwan

Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers

Identification of an Autophagy-Related lncRNA Prognostic Signature and Related Tumor Immunity Research in Lung Adenocarcinoma

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