RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating RNA splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of RNA methylation on tumor immunity. The primary types of RNA methylation encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), and N7-methylguanosine (m7G), and 3-methylcytidine (m3C). Compelling evidence underscores the involvement of RNA methylation in regulating the tumor microenvironment (TME). By affecting RNA translation and stability through the "writers", "erasers" and "readers", RNA methylation exerts influence over the dysregulation of immune cells and immune factors. Consequently, RNA methylation plays a pivotal role in modulating tumor immunity and mediating various biological behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed the mechanisms and functions of several RNA methylations, providing a comprehensive overview of their biological roles and underlying mechanisms within the tumor microenvironment and among immunocytes. By exploring how these RNA modifications mediate tumor immune evasion, we also examine their potential applications in immunotherapy. This review aims to provide novel insights and strategies for identifying novel targets in RNA methylation and advancing cancer immunotherapy efficacy.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. HCC has high rates of death and recurrence, as well as very low survival rates. N6-methyladenosine (m6A) is the most abundant modification in eukaryotic RNAs, and circRNAs are a class of circular noncoding RNAs that are generated by back-splicing and they modulate multiple functions in a variety of cellular processes. Although the carcinogenesis of HCC is complex, emerging evidence has indicated that m6A modification and circRNA play vital roles in HCC development and progression. However, the underlying mechanisms governing HCC, their cross-talk, and clinical implications have not been fully elucidated. Therefore, in this paper, we elucidated the biological functions and molecular mechanisms of m6A modification in the carcinogenesis of HCC by illustrating three different regulatory factors ("writer", "eraser", and "reader") of the m6A modification process. Additionally, we dissected the functional roles of circRNAs in various malignant behaviors of HCC, thereby contributing to HCC initiation, progression and relapse. Furthermore, we demonstrated the cross-talk and interplay between m6A modification and circRNA by revealing the effects of the collaboration of circRNA and m6A modification on HCC progression. Finally, we proposed the clinical potential and implications of m6A modifiers and circRNAs as diagnostic biomarkers and therapeutic targets for HCC diagnosis, treatment and prognosis evaluation.

Hepatocellular carcinoma (HCC) is one of the most lethal tumors in China and worldwide, although first-line therapies for HCC, such as atezolizumab and bevacizumab, have been effective with good results, the researches on new therapies have attracted much attention. With the deepening research on tumor immunology, the role and operation mechanism of immune cells in the tumor microenvironment (TME) of HCC have been explained, such as programmed cell death protein 1 (PD-1) binding to ligand could cause T cell exhaustion and reduce IFN-γ T cell secretion, cytotoxic T lymphocyte 4 (CTLA-4) and CD28 mediate immunosuppression by competing for B7 protein and disrupting CD28 signal transduction pathway, which also lays the foundation for the development and application of more new immune checkpoint inhibitors (ICIs). The biological behavior of various immune checkpoints has been proved in HCC, such as PD-1, programmed cell death ligand 1 (PD-L1), CTLA-4 and so on, leading to a series of clinical trials. Currently, FDA approved nivolumab, pembrolizumab and nivolumab plus ipilimumab for the treatment of HCC. However, the treatment of ICI has the disadvantages of low response rate and many side effects, so the combination of ICIs and various other therapies (such as VEGF or VEGFR inhibition, neoadjuvant and adjuvant therapy, locoregional therapies) has been derived. Further studies on immune checkpoint mechanisms may reveal new therapeutic targets and new combination therapies in the future.

The prognosis of colorectal cancer (CRC) is largely dependent on the early detection of hepatic metastases. With the advantages of nonradioactivity and the availability of multiple scanning sequences, the efficacy of magnetic resonance imaging (MRI) in the detection of colorectal liver metastases (CRLM) is not yet clear. We performed this meta-analysis to address this issue. PubMed, Embase, and the Cochrane Library were searched for studies reporting diagnostic performance of MRI for CRLM. Descriptive and quantitative data were extracted. The study quality was evaluated for the identified studies and a random effects model was used to determine the integrated diagnosis estimation. Meta-regression and subgroup analyses were implemented to investigate the potential contributors to heterogeneity. As a result, seventeen studies were included for analysis (from the year 1996 to 2018), comprising 1121 patients with a total of 3279 liver lesions. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.90 (95% confidence intervals (CI): 0.81–0.95), 0.88 (0.80–0.92), and 62.19 (23.71–163.13), respectively. The overall weighted area under the curve was 0.94 (0.92–0.96). Using two or more imaging planes and a quantitative/semiquantitative interpretation method showed higher diagnostic performance, although only the latter demonstrated statistical significance (P < 0.05). Advanced scanning sequences with DWI and liver-specific contrast media tended to increase the sensitivity for CRLM detection. We therefore concluded that contemporary MRI has high sensitivity and specificity for screening CRLM, especially for those with advanced scanning sequences. Using two or more imaging planes and adopting a quantitative/semiquantitative imaging interpretation may further improve diagnosis. However, the MRI results should be interpreted with caution because of substantial heterogeneity among studies.

Cancer stemness, mainly consisting of chemo-resistance, radio-resistance, tumorigenesis, metastasis, tumor self-renewal, cancer metabolism reprogramming, and tumor immuno-microenvironment remodeling, play crucial roles in the cancer progression process and has become the hotspot of cancer research field in recent years. Nowadays, the exact molecular mechanisms of cancer stemness have not been fully understood. Extensive studies have recently implicated that non-coding RNA (ncRNA) plays vital roles in modulating cancer stemness. Notably, N6-methyladenosine (m6A) modification is of crucial importance for RNAs to exert their biological functions, including RNA splicing, stability, translation, degradation, and export. Emerging evidence has revealed that m6A modification can govern the expressions and functions of ncRNAs, consequently controlling cancer stemness properties. However, the interaction mechanisms between ncRNAs and m6A modification in cancer stemness modulation are rarely investigated. In this review, we elucidate the recent findings on the relationships of m6A modification, ncRNAs, and cancer stemness. We also focus on some key signaling pathways such as Wnt/β-catenin signaling, MAPK signaling, Hippo signaling, and JAK/STAT3 signaling to illustrate the underlying interplay mechanisms between m6A modification and ncRNAs in cancer stemness. In particular, we briefly highlight the clinical potential of ncRNAs and m6A modifiers as promising biomarkers and therapeutic targets for indicating cancer stemness properties and improving the diagnostic precision for a wide variety of cancers.

Cancer immune checkpoint inhibitors (ICIs) have brought breakthroughs, but only about one‐third of cancer patients benefit from ICIs. In recent years, targeting non‐apoptotic regulated cell death (RCD) subtypes, such as ferroptosis, necroptosis, autophagy, cuproptosis, and pyroptosis, has emerged as a novel strategy in cancer therapy due to their ability to release damage‐associated molecular patterns (DAMPs), enhance antigen presentation, and remodel the tumor immune microenvironment, thereby activating anti‐tumor immune responses. A number of studies have shown that precise induction of these pathways by small molecules or nanoparticles can reverse the resistance to chemoradiotherapy and ICIs, promote the transformation of “cold tumors” to “hot tumors,” and ultimately establish durable immune memory. This article systematically reviewed the key mechanisms and immunomodulatory functions of five types of non‐apoptotic RCD (ferroptosis, necroptosis, autophagy, cuproptosis, and pyroptosis), discussed the related treatment strategies, and prospects for the future application in combination with existing immunotherapy.