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Open research questions in Immune cells in cancer

1,090 gap statements mined from Immune cells in cancer papers in our 7.9M-paper local library, which holds 3,679 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The mechanisms by which broad-spectrum antipathogens act are largely elusive. The effects of K21 on mitochondria and macrophage function are not well understood.

    Drug-induced metabolic remodeling promotes antimicrobial activity in macrophages and extends longevity in vivo · 2026 · DOI

  • Lack of understanding of the multiscale features of immunosuppression in solid tumors. Limited consideration of spatial effects, metabolic adaptation, and clinical implications in immunosuppression research. Need for a deeper understanding of the dynamic interplay between spatial effects, metabolic reprogramming, and immune regulation.

    Editorial: Spatial and metabolic dimensions of immunosuppression in the solid tumor microenvironment · 2026 · DOI

  • The existence of alternative pathways for macrophage development beyond the classical monocyte lineage is unclear. Prior work has focused on the role of monocytes in macrophage development, but the biology of other progenitor cells is less well understood. The discovery of EMPROR cells addresses this gap, revealing a new pathway for macrophage generation.

    A CD4-lineage erythro–myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation · 2026 · DOI

  • It highlights the need for more effective therapeutic strategies to target TAMs. The gap also includes the lack of understanding of the complex interactions between TAMs and tumor cells.

    Tumor-associated macrophage reprogramming in cancer: recent advances in resistance mechanisms and therapy · 2026 · DOI

  • The underlying molecular mechanisms of obesity-induced immunosuppression and its impact on cancer cell proliferation are not fully understood. There is a need to identify new biomarkers for cancer early diagnosis and improve therapeutic efficacy in obese patients.

    The Role of Obesity in the Regulation of Immunosuppressive Cell Infiltration and Immunosurveillance in Cancers · 2025 · DOI

  • The exact role of angiotensin II in the crosstalk between tumor-associated macrophages and breast cancer cells is not well understood. The effects of angiotensin II on macrophage polarization and breast cancer cell lines are not fully elucidated.

    Role of Renin–Angiotensin System and Macrophages in Breast Cancer Microenvironment · 2025 · DOI

  • The current understanding of macrophage functions in diabetic kidney disease is limited. There is a need to explore the polarization of macrophages and their role in the disease's progression. The therapeutic potential of regulating macrophage activity is not fully understood.

    Targeting Macrophages: Therapeutic Approaches in Diabetic Kidney Disease · 2024 · DOI

  • The role of endothelial mitochondria in melanoma progression is unclear. The mechanisms by which endothelial mitochondria affect melanoma cell growth and tumor progression are not well understood.

    Endothelial Mitochondria Transfer to Melanoma Induces M2-Type Macrophage Polarization and Promotes Tumor Growth by the Nrf2/HO-1-Mediated Pathway · 2024 · DOI

  • There is a need for a novel molecular biomarker to predict poor survival in gastric cancer patients. Current biomarkers are not sufficient to predict patient outcomes. The gap is the lack of understanding of the role of tumor and peritoneum-associated macrophage gene signature in gastric cancer.

    Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer · 2024 · DOI

  • Despite these insights, its roles in myeloid-derived suppressor cells, neutrophils, and other stromal subsets remain poorly understood.

    Progranulin and Inflammation‐Induced Cancer: An Important Player in the Tumor Microenvironment? · 2026 · DOI

  • However, it remains unclear whether this signaling pathway affects the polarization of TAMs in HCC.

    FGF19/FGFR4 axis drives immunosuppressive macrophage plasticity in hepatocellular carcinoma · 2026 · DOI

  • Remarkably, the human leukemic THP-1 cell line, the most prominent model for immune cell research questions, was demonstrated to be a subject of branched evolution through diverse cultivation conditions; however, little is known about its impact on THP-1 as monocyte model.

    Comparison of THP‐1 Subtypes Reveals Differences on Transcriptomic and Protein Expression Level Throughout Their Immunological Differentiation · 2026 · DOI

  • CD169+ cells represent a distinct subset of macrophages with potential immunomodulatory roles, but their function in colorectal cancer (CRC) progression remains unclear.

    Spatial Profiling and Prognostic Role of CD169+ Macrophages in Colorectal Cancer From Adjacent Nontumor Mucosa to Liver Metastasis · 2026 · DOI

  • Persistent HPV infection is a major risk factor for cervical cancer, but the immune mechanisms behind HPV‐induced tumor progression are not fully understood.

    HPV Infection Drives CXCL8 + Neutrophil‐Mediated Immune Suppression in Cervical Cancer · 2026 · DOI

  • Macrophage heterogeneity is increasingly recognized as an important feature of the gastric cancer tumor microenvironment, yet the macrophage states linked to poor outcome and the molecules connecting them to stromal remodeling remain incompletely defined.

    Integrated Single‐Cell and Spatial Transcriptomics Reveal SERPINE1 as a Key Link Between Macro_SPP1 Macrophages and Stromal Remodeling in Gastric Cancer · 2026 · DOI

  • The exact mechanism of the anti-tumorigenic effects of fluid shear stress is still not clear. The role of fluid shear stress in modulating macrophage polarization and its impact on breast cancer progression is not well understood.

    Fluid Shear Stress Modulates Inflammation in Breast Cancer Microenvironment · 2025 · DOI

  • Macrophages play essential roles in immune defense and tissue homeostasis, but the mechanisms underlying their colonization in the gut mucosa remain incompletely understood.

    Fibroblast-derived CSF1 maintains colonization of gut mucosal macrophage to resist bacterial infection · 2025 · DOI

  • Whether these roles are attributed to distinct subsets of macrophages or if macrophages retain a degree of plasticity in the intestine remains poorly understood.

    Tissue resident colonic macrophages persist through acute inflammation and adapt to aid tissue repair · 2025 · DOI

  • Further studies on the effects of K21 on other types of immune cells, - Investigation of the potential therapeutic applications of K21, - Elucidation of the molecular mechanisms underlying K21-induced…

    Drug-induced metabolic remodeling promotes antimicrobial activity in macrophages and extends longevity in vivo · 2026 · DOI

  • Further evaluation of the transcriptomic relevance of the upregulated genes and correlated genes, - Investigation of the biological basis of chronic wound persistence…

    Integrating bulk and single-cell RNA sequencing identifies and validates lipid metabolism-associated genes in diabetic foot ulcer · 2026 · DOI

  • To further determine how specific microenvironmental conditions alter the net impact of immune cells. To construct spatially resolved, cross-scale maps of tumor-immune ecosystems.

    Editorial: Spatial and metabolic dimensions of immunosuppression in the solid tumor microenvironment · 2026 · DOI

  • Future studies will be needed to dissect how EMPROR-and monocyte-derived macrophages partition among tissue niches - how local cues may shape their relative…

    A CD4-lineage erythro–myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation · 2026 · DOI

  • Integrate conventional clinical endpoints with TAM-specific pharmacodynamic measures, - Use biomarker-guided enrollment and longitudinal sampling to identify patients whose tumors are functionally dependent on the targeted macrophage program, - Investigate combination strategies with immunotherapy, cytotoxic therapy, and other…

    Tumor-associated macrophage reprogramming in cancer: recent advances in resistance mechanisms and therapy · 2026 · DOI

  • Determine if the classification of M2 macrophages can effectively target their pro-fibrotic activity - Investigate the potential synergistic relationship between macrophage subtypes - Further research on the role of M2 macrophages in treating kidney…

    Targeting Macrophages: Therapeutic Approaches in Diabetic Kidney Disease · 2024 · DOI

  • Investigate the underlying mechanisms of M2TS expression, - Validate the findings in a larger cohort of patients, - Explore the potential of M2TS as a therapeutic…

    Tumor and Peritoneum-Associated Macrophage Gene Signature as a Novel Molecular Biomarker in Gastric Cancer · 2024 · DOI

Most-cited papers in Immune cells in cancer

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Open questions raised by papers listed on this page include: (1) The effects of K21 on mitochondria and macrophage function are not well understood (“Drug-induced metabolic remodeling promotes antimicrobial activity in…”, 2026); (2) Lack of understanding of the multiscale features of immunosuppression in solid tumors (“Editorial: Spatial and metabolic dimensions of immunosuppression in the solid…”, 2026); (3) The existence of alternative pathways for macrophage development beyond the classical monocyte lineage is unclear (“A CD4-lineage erythro–myeloid progenitor within the adult bone marrow defines…”, 2026); (4) The gap also includes the lack of understanding of the complex interactions between TAMs and tumor cells (“Tumor-associated macrophage reprogramming in cancer: recent advances in…”, 2026); (5) Despite these insights, its roles in myeloid-derived suppressor cells, neutrophils, and other stromal subsets remain poorly understood (“Progranulin and Inflammation‐Induced Cancer: An Important Player in the Tumor…”, 2026). 1,090 gap statements have been mined from Immune cells in cancer papers in our 7.9M-paper local library, which holds 3,679 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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