[This corrects the article on p. 1369 in vol. 9, PMID: 28386362.].

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immune responses. Recent advances highlight the strong synergistic potential of combining epigenetic inhibitors with oncolytic viruses. This strategy enhances viral replication and tumor cell killing, reprograms the tumor microenvironment, and ultimately improves therapeutic efficacy. Consequently, the integration of epigenetic modulators with OV therapy represents a promising frontier in oncology. This review comprehensively examines epigenetic inhibitors, with emphasis on their combined application with oncolytic viruses for cancer treatment.

Cancer treatment remains in need of novel therapeutic strategies to improve patient outcomes. Cuproptosis, a recently identified form of immunogenic cell death, is recognized for its significant anticancer potential. However, most cuproptosis-based strategies are still in the preclinical stage, and the limited clinical trials conducted thus far have yielded unsatisfactory results. Cancer cells develop resistance to cuproptosis through mechanisms such as metabolic reprogramming or altered signaling pathways. Investigating how to overcome this resistance is therefore crucial for advancing cuproptosis-based therapies. This review summarizes cellular copper homeostasis and its regulation, compares cuproptosis with other immunogenic cell death modalities, and discusses the factors governing cuproptosis sensitivity. From a translational perspective, this review highlights emerging nanomedicine strategies to enhance cuproptosis sensitivity through metabolic vulnerability targeting and pharmacological reversal of resistance mechanisms. Finally, this review envisions the broader therapeutic potential of cuproptosis modulation beyond oncology. These advances may ultimately redefine clinical paradigms, offering hope for meaningful survival extensions and improved quality of life for cancer patients.

Malignant tumors remain a leading cause of premature death worldwide, with disproportionately increasing burdens in resource-limited regions. Although immune checkpoint blockade (ICB) has emerged as a transformative cancer therapy, its efficacy is often limited by the immunosuppressive tumor microenvironment (TME). Leveraging iron as the most abundant bioactive transition metal in Earth's crust, we report F-Fe, a complex IV-targeted carbon monoxide-releasing molecule (CORM) that is activated by a clinically approved dental light-curing unit to induce pyroptosis for reprogramming the TME. We developed a bioinspired delivery system named GLEAM to facilitate clinical applications that adhere to tissue surfaces while channeling light into deeper tissue for on-target CO release, simultaneously providing real-time visual feedback for treatment monitoring. Murine oral and breast cancer models validated the therapeutic efficacy, showing significant tumor suppression and TME remodeling. When combined with anti-PD-1 antibody (aPD-1) therapy, it markedly suppressed metastasis, prevented recurrence, and prolonged survival. Our findings suggest that Fe-based small molecules with biomimetic delivery can leverage dental light to boost ICB efficacy, offering a sustainable and translational approach to tumor treatment.

Cancer immunotherapy holds promise for improving the efficacy of cancer treatment; however, low response rates remain a considerable challenge. Photodynamic therapy has a potential to be effective in immunotherapy, but it is limited by the inabilities to target tumor and limitation of reactive oxygen species (ROS) generation by hypoxia. Here, mitochondria-targeted zinc phthalocyanines (ZnPcs) are developed to precisely induce pyroptosis and activate immune responses. Cationic moieties incorporated in the ZnPc core allow strong localization in the mitochondrion and avoid aggregation of ZnPc, which serves as the highest site-specific production of ROS through the irradiation process. ZnPc-4 is among the synthesized derivatives that inhibit oxidative phosphorylation, relieving hypoxia and increasing type I/II ROS to cause mitochondrial dysfunction, which eventually triggers pyroptosis. Encapsulation of ZnPc-4 within DSPE-PEG2000-cRGDfk nanoparticle (ZnPc-NP) enhances its tumor-targeted capability and biocompatibility. In vivo, ZnPc-NP triggers immunogenic pyroptosis, eliciting potent anti-tumor immunity. In addition, ZnPc-NP combines with αPD-1, significantly inhibiting tumor metastasis and recurrence. This study establishes a dual-targeted photodynamic platform that overcomes microenvironmental constraints to potentiate cancer immunotherapy.

As the threat of cancer to humanity continues to intensify, immunotherapy has emerged as a promising novel approach in cancer treatment. However, the efficacy of existing immunotherapy varies and needs to be improved urgently. Tissue-resident memory T (TRM) cells, a subset of T cells, have typical tissue-residency characteristics and formidable antitumor potential, which may be a latent enhancer for cancer immunotherapy. Besides, TRM cells are more readily modulated in the process of immunotherapy, compared to other T cell subsets present in the tumor microenvironment. This review summarizes the molecular phenotypes of TRM cells, introduces the relationship between TRM cells and cancer immunology, and proposes a range of potential immunotherapeutic strategies targeting TRM cells. Particularly, this review critically evaluates current clinical strategies and research aimed at modulating TRM cells. These insights are intended to provide new directions for tuning TRM for advancing cancer immunotherapy.

Cancer immunotherapy, particularly using oncolytic viruses (OVs), has been recognized as a promising approach for treating malignant tumors because of its dual ability to selectively kill tumor cells and activate antitumor immunity. However, OV monotherapy faces inherent challenges, including suboptimal viral delivery efficiency, an immunosuppressive tumor microenvironment, and premature systemic-immune clearance. Recent breakthroughs in biomaterials have provided new avenues for optimizing oncolytic virotherapy by overcoming these limitations using innovative system designs. In this review, we systematically examined the synergistic combination of biomaterials with OVs to enhance cancer immunotherapy, emphasizing two major categories: nanomaterial-based carriers and cell-derived materials. Intelligent biomaterial delivery systems can spatiotemporally protect viruses from immune clearance and enable targeted accumulation and controlled release. Functionalized biomaterials can serve as immunomodulators or drug carriers that synergize with OVs to remodel the tumor microenvironment. Particular focus was placed on biomimetic virus-like nanoparticles, and their design principles, mechanisms, and applications were critically discussed in this review. Finally, we summarize the potential challenges and prospects of combining biomaterials with OVs to enhance cancer immunotherapy, paving the way for a clinical translation of this approach.

The intravenous delivery of oncolytic viruses (OVs) often demonstrates limited therapeutic efficacy due to rapid clearance by peripheral neutralizing antibodies and poor penetration into deeper tumor regions. To overcome these bottlenecks, we report a triple-cascade responsive pneumatic nanomotor (HLNO) designed for systemic delivery of the oncolytic herpes simplex virus (oHSV). The HLNO nanomotor utilizes a hierarchically structured core-shell design featuring an oHSV core encapsulated within a glutathione-responsive liposome layer and hyaluronic acid outer shell while incorporating the pH-sensitive nitric oxide (NO) donor. This system enables immune evasion of oHSV in peripheral circulation while demonstrating programmable activation that specifically responds to tumor microenvironment stimuli. It is noteworthy that the HLNO nanomotor utilizes NO-propelled active motion under acidic conditions to enhance extravasation and tissue deep penetration, followed by hyaluronidase-mediated deshielding and glutathione-triggered oHSV release. Then, the HLNO nanomotor activates the caspase-3/GSDME pathway to induce immunogenic pyroptosis, which enhances antitumor immunity by increasing CD8+ T cell infiltration and M1-like macrophage polarization while driving vascular normalization and alleviating tumor hypoxia. By integrating immune shielding with cascade-responsive release, this platform addresses key limitations of systemic OVs delivery, offering an approach to enhance immunotherapy efficacy in immunologically "cold" tumors.

Following the publication of the above paper, the authors contacted the Editor to explain that they had made a couple of inadvertent errors in assembling the data in Figs. 1B and 2B. Specifically, the following issues were identified: first, the immunohistochemical staining images representing CD31 in Fig. 1B on p. 3434 were chosen from the wrong dataset; secondly, the immunohistochemical staining images representing HIF‑1α in Fig. 2B on p. 3435 were similarly included in this figure incorrectly. After having performed an independent analysis of these data in the Editorial Office, it came to light that certain of the data featured in Fig. 2B had been submitted for publication at around the same time in an article featuring some of the same authors to the journal PLoS One. However, the authors were able to consult their original data, and the revised versions of Figs. 1 and 2, now featuring all the correct data for Figs. 1B and 2B, are shown on the next two pages. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 12: 3432‑3438, 2015; DOI: 10.3892/mmr.2015.3815] .

[This corrects the article on p. 162 in vol. 7, PMID: 25755838.].

While immunotherapy has demonstrated remarkable therapeutic potential in certain malignancies, its overall clinical efficacy remains suboptimal. Emerging evidence indicates that the tumor microenvironment (TME) plays a pivotal role in determining immunotherapy response, with tumor-associated macrophages (TAMs) - the predominant immune cell population within TME - being closely associated with poor prognosis, metastatic progression, and therapeutic resistance. Traditionally, macrophages are classified into two primary activation states: the pro-inflammatory M1 (classically activated) phenotype and the anti-inflammatory M2 (alternatively activated) phenotype. However, this binary classification system fails to fully capture the functional complexity and phenotypic plasticity of TAMs. This comprehensive review critically examines TAM heterogeneity and explores emerging subtyping paradigms beyond conventional M1/M2 dichotomization. Furthermore, we systematically examine three principal therapeutic strategies: recruitment inhibition, TAM depletion, and phenotypic reprogramming, emphasizing their synergistic potential with existing immunotherapies. These multifaceted approaches provide novel insights for developing combination therapies to overcome current limitations in cancer treatment.

While cancer immunotherapy has transformed clinical management for cancer patients, its low response rates remain a critical challenge to be addressed. Tumor immune evasion now extends beyond the tumor microenvironment (TME), as advanced tumors induce extramedullary hematopoiesis (EMH) in the spleen, leading to a substantial expansion of erythroid progenitor cells (EPCs) with potent immunosuppressive capacity. EPCs are typically transient populations in erythroid maturation and differentiation; however, under tumor burden, they undergo profound metabolic reprogramming that exacerbates their immunosuppressive effects. This review examines the role and mechanisms of tumor-hijacked metabolic reprogramming in EPCs and provides strategies for targeting this reprogramming to potentiate cancer immunotherapy. In particular, we synthesize the metabolic interplay between EPCs, tumor cells, and immune cells, integrating EPC metabolic reprogramming with established concepts of tumor cell metabolism and immunometabolism. Furthermore, this review outlines future directions for the field, including multi-modal approaches to decipher the mechanisms of EPC metabolic reprogramming, biomarker development, and metabolism-based targeted therapies, all aimed at improving survival and prognosis for cancer patients.

Cancer remains a leading cause of human mortality worldwide, imposing a substantial public health burden. A deep understanding of the tumor microenvironment (TME) is essential for improving cancer care. Erythroid progenitor cells (EPCs) were traditionally viewed solely as intermediates in erythropoiesis; however, growing evidence indicates their active involvement in cancer progression and immune evasion. Research on EPCs increasingly utilizes omics sequencing technologies. Multi-omics strategies in particular enable in-depth investigation of the functional mechanisms of EPCs and their interactions with tumor and immune cells. This review examines various omics methodologies applied to EPCs from an oncology perspective, including transcriptomics, proteomics, epigenomics, and metabolomics, while critically assessing the advantages and limitations of each approach. Furthermore, it synthesizes how the integration of multiple omics technologies provides a more comprehensive view of EPC biology, particularly through complementary data modalities. This review also discusses artificial intelligence (AI)-powered multi-omics integration strategies and explore the translational potential of EPC-focused research in advancing cancer therapeutics from bench to bedside.

Cancer immunotherapy has revolutionized oncology by harnessing the immune system to combat malignant tumors, driving significant advancements in cancer treatment. However, due to the complex interplay between tumor cells and immune cells, many patients fail to achieve durable responses. Mast cells are bone marrow-derived immune cells and a crucial component of the innate immune system. Previously, mast cells were primarily recognized for their roles in allergic and inflammatory responses. In recent years, increasing attention has been directed toward their dual functions in the tumor microenvironment during cancer progression, highlighting the potential of mast cell-targeted strategies in cancer immunotherapy. This review summarized recent advances about the dual role of mast cells in the tumor microenvironment. At the same time, this review further evaluates the translational potential of mast cells as predictive markers and innovative therapeutic targets for cancer immunotherapy. By elucidating these mechanisms, this review aims to bridge the gap between preclinical insights and clinical applications, offering a roadmap for mast cell-centric approaches to overcome resistance and improve outcomes in cancer immunotherapy.

A central obstacle in cancer immunotherapy is the "cold" tumor, characterized by limited immune infiltration, which renders it largely unresponsive to treatment. Tertiary lymphoid structures (TLS), functioning as ectopic immune niches, can convert these cold tumors into "hot" ones by supporting antigen presentation, lymphocyte activation, and coordinated immune responses. Therefore, strategies to induce TLS formation hold significant therapeutic promise. Recent studies have explored a range of biomaterial systems designed to orchestrate the formation of TLS within the tumor microenvironment. This encompasses synthetic biomaterial platforms (nanocarriers, stimulus-responsive hydrogels, programmable 3D scaffolds, and mesoporous materials), natural and bioderived systems (organoids and exosomes), as well as emerging bioactive entities (engineered immune cells, oncolytic viruses, and bacteria). This review outlines the cellular composition, maturation process, and immunological functions of TLS, highlights diverse biomaterial platforms facilitating TLS formation, and summarizes translational challenges, including biosafety, standardization, and scalability. Inducible TLS (iTLS) provide a potent means to remodel the tumor immune microenvironment, offering exciting opportunities for advanced cancer immunotherapy.

Cancer immunotherapy has markedly improved clinical outcomes for cancer patients. However, its broad application is constrained by low response rates, which limit therapeutic benefits to only a subset of individuals. A deeper understanding of the tumor microenvironment (TME) and the interactions between tumor and immune cells is crucial for overcoming resistance. In this context, the reprogramming of erythroid progenitor cells (EPCs) within the TME has emerged as an important mechanism of immunotherapy resistance. EPCs, a key population in erythroid differentiation, undergo epigenetic reprogramming that underlies various physiological and pathological states. Through epigenetic modifications, EPCs may interact with immune cells and thereby promote tumor immune evasion. This review summarizes EPC reprogramming in the TME from an epigenetic perspective and explores their crosstalk with tumor and immune cells. It also evaluates the therapeutic potential of epigenetic drugs targeting EPCs and discusses future research directions focused on reversing pathological epigenetic reprogramming in EPCs to enhance immunotherapy efficacy. These advances hold significant potential for optimizing clinical cancer care paradigms and improving patient prognosis.

Chemoresistance remains a major barrier to effective cancer treatment, leading to tumor recurrence and high mortality. Developing strategies to combat chemoresistant tumors is therefore an urgent challenge. Here, we report a covalent organic framework (COF) nanomedicine, 3N-DPQ-COF, designed to target chemoresistant cancers. Mechanistic studies reveal that 3N-DPQ-COF accumulates efficiently in resistant tumor cells and suppresses cancer stemness in 4T1 and CT26 models, outperforming doxorubicin. Moreover, 3N-DPQ-COF promotes CD8+ T-cell infiltration and reduces the number of immunosuppressive erythroid progenitor cells and myeloid-derived suppressor cells, thereby remodeling the tumor microenvironment (TME) and inducing GSDME-dependent pyroptosis. Remarkably, even without checkpoint blockade, 3N-DPQ-COF suppresses metastasis and recurrence in chemoresistant 4T1 tumors, achieving >90% tumor inhibition and cure rates exceeding 80%. This study highlights the potential of AIEgen-based COF nanomedicines for overcoming chemoresistance through concurrent modulation of tumor stemness, pyroptosis, and immune activation.

[This corrects the article on p. 507 in vol. 9, PMID: 28337279.].

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates formed by lymphocytes and antigen-presenting cells within chronic inflammatory microenvironments or tumor microenvironments (TMEs), and their initiation phase is a critical step for mounting an effective antitumor immune response. TLS initiation depends on the interplay between lymphoid tissue inducer cells and lymphoid tissue organizer cells and is finely regulated by multiple cytokines and chemokines. This review systematically summarizes the key triggers and signaling networks driving TLS initiation, elucidating how TLSs reshape the TMEs, facilitate antigen presentation, and recruit immune cells to enhance antitumor immune responses. Furthermore, potential strategies to modulate TLS initiation are discussed, along with the emerging role of TLSs as promising targets in cancer immunotherapy.