Trends in cancer最新文献

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas driven by distinct biological pathways. Although historically divided into two major subtypes on the basis of putative cell of origin, detailed genomic analyses have revealed additional classifications with prognostic implications. Additionally, the lymphoma microenvironment adds a layer of complexity distinct from genetic subclassifications and influences disease trajectory and response to therapies. Herein, we review the emerging roles of immune-based therapies to address this complex interplay between intrinsic genetic drivers and the surrounding tumor microenvironment in DLBCL.

The dreadful liaison between platelets and tumor cells was discovered half a century ago. Since then, a plethora of studies have characterized the contribution of platelets to primary tumor development, survival of circulating tumor cells in the bloodstream, and metastatic seeding and outgrowth. Yet, although these provided a deep understanding of how platelets shape cancer progression, the field suffers from a lack of additional knowledge required to design efficient therapeutic strategies. Here, we aim to summarize recent discoveries that identify new ways in which platelets shape metastasis beyond their initial intravascular role. We further discuss platelet-borne molecular targets that could represent new avenues for therapeutically targeting platelets' contribution to metastasis.

Myeloid cell leukemia 1 (MCL-1), an antiapoptotic protein, belongs to the BCL-2 protein family and is an extensively studied anticancer target. MCL-1 inhibitors have been in development for decades but fall short on efficacy, toxicity, and side-effects. Recently, Brinkmann et al. shed light on the apoptosis-unrelated function of MCL-1 and its physiological role that could critically lead to MCL-1 inhibitor development.

Phagocytosis upregulation plays a crucial role in bridging to adaptive immunity for cancer immunotherapy. However, current approaches to modulating phagocytosis are beneficial to certain types of cancer only. In this Forum paper, we will highlight how nanoengineering can overcome the current limitation of phagocytosis-mediated cancer immunotherapy.

Targeting negative regulators of immunity with immune-checkpoint inhibitors (ICIs) has led to significant survival benefit in patients with various cancer entities. ICI therapy disrupts mechanisms of immune tolerance, which induces inflammatory toxicities in different target organs, summarized as immune-related adverse events (irAEs) in some patients. ICI-colitis relies on the activation of intestinal tissue-resident memory T cells (T_RM cells) and is one of the most frequently observed immune-related toxicities; it can be fatal if untreated. The disease is associated with highly cytotoxic intestinal T cells and inflammatory myeloid activation. Current clinical management relies on broad immunosuppression, potentially reducing antitumor immunity. Ideal future therapies for irAEs will uncouple immunosuppressive activities in the inflamed target organ and the tumor microenvironment.

Most patients with advanced cancer suffer from cachexia, a complex metabolic disorder characterized by unintentional body weight loss that diminishes their quality of life and reduces the effectiveness of therapies. Currently, effective treatments for cachexia remain elusive. Growth differentiation factor 15 (GDF15) is a nonspecific blood biomarker of cancer, hyperemesis gravidarum, and various chronic diseases. GDF15 acts through GDNF family receptor α-like (GFRAL) receptors in the hindbrain to influence food intake, nausea, body weight, and insulin sensitivity. In this review we synthesize the current literature on the role of GDF15 in regulating metabolism and immunosuppression, and elucidate how these processes impact on cancer progression. We highlight recent clinical trials demonstrating that targeting GDF15 can overcome resistance to immunotherapy and increase physical activity, appetite, and weight gain in cancer patients.

Cancer immunotherapy has transformed treatment but faces challenges such as immune evasion and toxicity. Polo-like kinases (PLKs), frequently dysregulated in tumors, are emerging as key immune modulators. Combining PLK inhibition with immunotherapy may overcome resistance, enhance antitumor responses, and improve clinical outcomes, offering an optimally efficient strategy for cancer treatment.

Retrotransposons are mobile repetitive elements that constitute around 43% of the human genome. Normally silenced through epigenetic mechanisms, retrotransposons can become reactivated in response to various stimuli, producing immunogenic DNA, RNA, and peptides that trigger innate and adaptive immune responses. In normal hematopoiesis, retrotransposon reactivation can drive inflammatory signaling responses, which support stem cell activity, influencing hematopoietic stem and progenitor cell (HSPC) regeneration. In hematological cancers, their reactivation can alter the tumor microenvironment and promote immune evasion. Here, we highlight the complex interactions between retrotransposons, hematopoiesis, and immune modulation. We also emphasize the therapeutic potential of targeting retrotransposons, while addressing critical knowledge gaps in retrotransposon-driven immune modulation across both health and disease.

Adoptive cell therapies (ACTs), such as chimeric antigen receptor (CAR)-T cell therapy, have revolutionized cancer treatment, especially for hematological cancers. However, patient responses vary considerably. Emerging research reveals a striking influence of time of day (ToD) on ACT efficacy. Administering ACT during the early behavioral active phase enhances tumor control and reduces toxicity in preclinical models, an effect linked to the circadian clock. Latest clinical data also point to ToD effects in the cancer setting. In this opinion article we explore current insights and discuss the emerging underlying mechanisms. We propose that integrating ToD into clinical practice could represent a powerful yet easily implementable therapeutic regimen to improve efficacy and safety of ACT.

Chimeric antigen receptor (CAR)-T cell therapy has shown significant clinical benefit in hematologic malignancies but remains less effective in solid tumors due to multiple barriers, including limited tumor infiltration, immunosuppressive microenvironments, and heterogeneity or imperfect specificity in tumor-antigen expression. 'Armoring' CAR-T cells to express chemokine receptors, enzymes that degrade extracellular matrix components, proinflammatory cytokines, or factors that modulate immunosuppressive signals could empower CAR-T cells to overcome barriers associated with solid tumors. However, translating promising preclinical results into reliable clinical benefit for patients with solid tumors remains challenging. This review critically examines emerging CAR-T cell armoring approaches and highlights key translational hurdles and the need for innovations in human-relevant disease models, safety designs, and treatment strategies for effective translation.