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Open research questions in Immune cells in cancer

324 unresolved questions extracted from the limitations and future-work sections of 606 Immune cells in cancer papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • bulk RNA-seq exhibits certain deficiencies including low precision and limited resolution in discerning heterogeneous cell populations, - the study does not provide a comprehensive analysis of the molecular mechanisms underlying immune cell migration, - the role of other factors such as age and tissue-specific adhesion molecules in immune cell migration is not fully understood

    Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets · 2026 · DOI

  • further studies are needed to elucidate the molecular mechanisms underlying immune cell migration, - investigation of the role of age and tissue-specific adhesion molecules in immune cell migration, - development of new techniques for tracking immune cell migration with higher precision and resolution

    Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets · 2026 · DOI

  • further exploration of the role of Toll-like receptors in the pathogenesis of COVID-19, - investigation of the mechanisms underlying the association between monocyte subsets and COVID-19 outcomes, - development of strategies to improve long-term protection and vaccine effectiveness

    Early monocyte subset signatures predict outcomes in unvaccinated COVID-19 patients · 2026 · DOI

  • The study identifies a gap in understanding the immune response to SARS-CoV-2 infection, particularly in unvaccinated patients. The study aims to address this gap by evaluating the profiles of monocytes and their receptor expression in unvaccinated COVID-19 patients.

    Early monocyte subset signatures predict outcomes in unvaccinated COVID-19 patients · 2026 · DOI

  • Further study of the role of MGST3 in atherosclerosis, - Investigation of the mechanisms by which MGST3 influences mitochondrial health, - Examination of the potential therapeutic applications of targeting MGST3

    MGST3 defines a mitochondrial-health-associated M2 macrophage state in atherosclerosis: integrative multi-omics, single-cell mediation, and functional validation · 2026 · DOI

  • The mitochondrial genes that shape disease-relevant macrophage states in atherosclerosis are poorly defined. The role of MGST3 in mitochondrial health within M2-like macrophages is unknown.

    MGST3 defines a mitochondrial-health-associated M2 macrophage state in atherosclerosis: integrative multi-omics, single-cell mediation, and functional validation · 2026 · DOI

  • the complexity of the tumor microenvironment - the heterogeneity of macrophage subtypes in CRC - the need for a framework to interpret the immune context of risk groups

    Integrated single-cell and bulk tissue analyses reveal distinct macrophage subtypes and a candidate prognostic signature in colorectal cancer: implications for tumor immune characterization · 2026 · DOI

  • the heterogeneity of macrophage subtypes in CRC is not well understood - there is a gap between CRC macrophage subtype heterogeneity and prognostic information - the role of macrophage-related genes in CRC is not fully elucidated

    Integrated single-cell and bulk tissue analyses reveal distinct macrophage subtypes and a candidate prognostic signature in colorectal cancer: implications for tumor immune characterization · 2026 · DOI

  • One challenge is the complexity of the tumor immune microenvironment, which can make it difficult to understand the effects of SYK inhibition. Another challenge is the need to develop effective therapeutic strategies that target SYK in breast cancer. A technical challenge is the requirement for specialized instruments and reagents, such as the Small Animal Radiation Research Platform (SARRP) and fostamatinib.

    Targeting SYK enhances responses to radiotherapy and PD-1 blockade with myeloid immune remodeling in breast cancer · 2026 · DOI

  • Direct R406 exposure and SYK target engagement were not measured under the experimental conditions, - The study used a limited number of mice (N = 6 for control group, N = 7 mice for treatment group), - The study focused on a specific type of breast cancer (TNBC)

    Targeting SYK enhances responses to radiotherapy and PD-1 blockade with myeloid immune remodeling in breast cancer · 2026 · DOI

  • A comprehensive synthesis of metal-phenolic network designs tailored specifically to the distinct pathological mechanisms underlying brain disorders is currently lacking. The clinical translation of metal-phenolic networks is hindered by uncertainties in long-term biosafety and in vivo metabolism, metal-specific neurotoxicity, and coordination-stability-governed metal release kinetics.

    Mechanism-Driven Design of Metal–Phenolic Networks: From Precision Assembly to Multidimensional Synergistic Therapy for Brain Diseases · 2026 · DOI

  • The complexity of the immunosuppressive microenvironment of gastric cancer. The need to develop effective therapeutic strategies to target CLEVER-1+ macrophages. The challenge of translating preclinical findings to clinical applications.

    CLEVER-1+ tumor-associated macrophages in gastric cancer immunotherapy resistance: integrating metabolic reprogramming and immunosuppression · 2026 · DOI

  • The functional link between FABP5 and lipid uptake requires investigation - The relationship between CLEVER-1 and glucose metabolism remains an open question - Direct measurements of glycolysis, such as lactate production or extracellular acidification rate, were not performed - The study lacks direct functional validation in CLEVER-1+ TAMs from GC

    CLEVER-1+ tumor-associated macrophages in gastric cancer immunotherapy resistance: integrating metabolic reprogramming and immunosuppression · 2026 · DOI

  • Exploring the correlation between neutrophils and cancer - Investigating the molecular mechanisms of neutrophils infiltrating the central nervous system - Studying the role of neutrophils in cancer immunotherapy

    Neutrophils in glioma microenvironment: from immune function to immunotherapy · 2024 · DOI

  • Further study on ROS generation and phagocytosis is required, - Study of specific macrophage activity is of especially importance

    Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages · 2024 · DOI

  • Little is known about how the polarization modulates macrophage functions. There is a lack of understanding of the mechanical properties of macrophages and how they differ between M0 and polarized cells.

    Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages · 2024 · DOI

  • The exclusion of CD8-positive T cells from the tumor microenvironment. The inhibition of CD8-positive T cell infiltration by CAFs. The need to identify concomitant drugs that enhance the efficacy of cancer immunotherapy in CRC.

    Pexidartinib and Immune Checkpoint Inhibitors Combine to Activate Tumor Immunity in a Murine Colorectal Cancer Model by Depleting M2 Macrophages Differentiated by Cancer-Associated Fibroblasts · 2024 · DOI

  • The study was conducted in a mouse model, - The study had a limited number of human CRC samples, - The study did not investigate the long-term effects of the combination therapy

    Pexidartinib and Immune Checkpoint Inhibitors Combine to Activate Tumor Immunity in a Murine Colorectal Cancer Model by Depleting M2 Macrophages Differentiated by Cancer-Associated Fibroblasts · 2024 · DOI

  • leveraging MPNs to inhibit NETs represents a highly promising therapeutic direction for the treatment of brain diseases

    Mechanism-Driven Design of Metal–Phenolic Networks: From Precision Assembly to Multidimensional Synergistic Therapy for Brain Diseases · 2026 · DOI

  • The impact of environmental materials on macrophage function in host defense is not well understood. There is a need to investigate the effects of these materials on macrophages and their defense functions.

    Plasma membrane damage by environmental materials enhances cell-cell fusion and impairs defense functions of macrophages · 2026 · DOI

  • Cancer-associated fibroblasts (CAFs) are major regulators of the tumor microenvironment, yet how distinct CAF states suppress innate immunity in HER2-low breast cancer remains poorly understood.

    A stromal metabolic program suppresses NK-cell immunity to drive tumor progression in HER2-low breast cancer · 2026 · DOI

  • The importance of these variables, although well-established in solid tumors, remains elusive in the context of hematological malignancies.

    Nanoparticle size governs engagement with myeloid cells and hitchhiking to hematopoietic organs in myeloproliferative neoplasms · 2026 · DOI

  • Purpose Tumors are often framed as unresolved wounds, but the extent to which independently defined physiological repair programs are recontextualized across cancers remains uncertain.

    A frozen human wound-repair reference reveals heterogeneous tumor niches and conditional immunotherapy associations · 2026 · DOI

  • Macrophage abundance is regulated by pathways controlling survival and proliferation, yet the genetic determinants of macrophage fitness remain poorly understood.

    High-resolution CRISPR/Cas9 screens identify PAK2 as a suppressor of macrophage proliferation · 2026 · DOI

  • The model reproduced experimentally observed macrophage recruitment and phenotype dynamics but demonstrated that recurrent recruitment, impaired inflammatory resolution, and adaptive immune bias were insufficient to reproduce the recurrent macrophage ecology.

    A Latent Inflammatory Tissue-State Variable Mechanistically Links Radiotherapy-Induced Immune Remodeling to Recurrent Tumor Permissiveness · 2026 · DOI

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324 open questions have been extracted from the limitations and future-work passages of 606 Immune cells in cancer papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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