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Open research questions in Cancer Immunotherapy and Biomarkers

2,273 gap statements mined from Cancer Immunotherapy and Biomarkers papers in our 7.9M-paper local library, which holds 9,870 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

  • Further studies are needed to validate the prognostic value of LIPI in patients with advanced NSCLC. Research should investigate the prognostic contribution of LIPI in combination with other biomarkers. Studies should explore the potential of LIPI to guide treatment decisions in clinical practice.

    Prognostic Value of the Lung Immune Prognostic Index in Advanced Non-Small Cell Lung Cancer Treated with Nivolumab: A Real-World Analysis Beyond PD-L1 Expression · 2026 · DOI

  • The benefit of immune checkpoint inhibitors in advanced NSCLC is not uniform. Tumor-based markers such as PD-L1 expression do not fully capture the complexity of treatment outcomes. There is a need for reliable and easily applicable biomarkers in daily oncology practice.

    Prognostic Value of the Lung Immune Prognostic Index in Advanced Non-Small Cell Lung Cancer Treated with Nivolumab: A Real-World Analysis Beyond PD-L1 Expression · 2026 · DOI

  • The study notes that the association between vonoprazan and anti-VEGF therapy may differ according to tumor type. The paper highlights the need for prospective clinical trials to evaluate the interaction between vonoprazan and anti-VEGF therapy. The study acknowledges the complexity of the gut microbiome and its role in modulating systemic anti-tumor immunity.

    Beyond gastric acid: pharmacologic modulation of the tumor microenvironment by vonoprazan and its drug-interaction implications for chemotherapy and immunotherapy · 2026 · DOI

  • It highlights the need to investigate the CEMIP-STAT3 axis and its role in immunosuppression.

    Immune Cell Landscape in the NSCLC Tumour Microenvironment: Molecular Dysregulation, Crosstalk and Insights into the CEMIP-STAT3-Mediated Immunosuppressive Axis · 2026 · DOI

  • It highlights the need for prompt therapeutic intervention due to the slow response to treatment. The paper also notes the challenge of diagnosing ICI-C due to its rare occurrence and non-specific symptoms.

    Case Series: Severe cholangitis as an immune checkpoint inhibitor induced adverse event in four cases: management and treatment options including tocilizuab and ursodeoxycholic acid · 2026 · DOI

  • Disease progression remained a concern, highlighting the need for optimized patient selection. The use of immune checkpoint inhibitors in HIV-associated cancers raises unique immunological considerations. HIV infection leads to chronic immune activation, CD4+ T-cell depletion, and functional impairment of cytotoxic T-lymphocytes, all of which can compromise effective antitumor immunity.

    Safety and Efficacy of Immune Checkpoint Inhibitors in Human Immunodeficiency Virus-Associated Cancer: A Systematic Scoping Review · 2025 · DOI

  • The paper identifies challenges in diagnosing radiation recall pneumonitis, including the need for clinical and imaging correlation. The paper highlights the challenge of managing opportunistic infections in immunocompromised patients.

    Radiation Recall Pneumonitis with Pneumocystis jirovecii Superinfection and Treatment Induced Hyponatremia in a Patient with Non-Small-Cell Lung Cancer · 2025 · DOI

  • There is a need for additional clinical studies and practical insights into immune-related adverse events. There is a need for the development of biomarkers for predicting immune toxicities. The diagnosis of immune-related adverse events can be challenging due to nonspecific signs and symptoms.

    Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations · 2024 · DOI

  • The need to consider tumor heterogeneity in immunotherapy treatment. The challenge of identifying biomarkers for patient stratification and personalized treatment.

    Immunotherapy and Cancer: The Multi-Omics Perspective · 2024 · DOI

  • Randomized clinical trials are complex and expensive, and can expose large populations of patients to unproven therapies. There is a clear difficulty in patient selection and monitoring, which contributes to significant failure rates. The lack of personalized medicine approaches in immunotherapy.

    Recent Advances in Artificial Intelligence to Improve Immunotherapy and the Use of Digital Twins to Identify Prognosis of Patients with Solid Tumors · 2024 · DOI

  • The clinical relevance of Spark-like T cells in non-small cell lung cancer is not well understood. Conventional predictive biomarkers do not fully capture the complex functional heterogeneity of tumor-infiltrating T cells. There is a need for novel biomarkers to improve patient stratification and predict immunotherapy response.

    Spark-like T cell represents a novel functional state of CD8+T cells associated with anti-PD-1 immunotherapy response and clinical prognosis in non-small cell lung cancer · 2026 · DOI

  • Previous Phase II trials have shown promising response rates, warranting further investigation through a randomised, placebo-controlled Phase III trial.

    Phase III Study Investigating the Safety and Efficacy of TM5614 in Combination With Nivolumab for the Treatment of Unresectable Malignant Melanoma: Protocol · 2026 · DOI

  • Combined RORgamma inhibition and PD-L1 blockade improves hepatic tumour control in preclinical HCC and warrants further investigation.

    Novel retinoic acid receptor-related orphan receptor gamma inverse agonist enhances checkpoint blockade in hepatocellular carcinoma: a preclinical mouse study · 2026 · DOI

  • Neutrophil-associated inflammation is associated with poor outcomes in hepatocellular carcinoma (HCC), but tumour-intrinsic regulators of neutrophil recruitment and checkpoint response remain unclear.

    Novel retinoic acid receptor-related orphan receptor gamma inverse agonist enhances checkpoint blockade in hepatocellular carcinoma: a preclinical mouse study · 2026 · DOI

  • ICOS, an inducible co-stimulatory receptor enriched on activated regulatory T cells (Tregs), represents a potential route of such immune regulation, but its role in breast cancer immunotherapy remains unclear.

    ICOS blockade alleviates immune suppression in breast tumor microenvironment · 2026 · DOI

  • Whether this reflects a failure to activate antitumor immunity or a failure to direct it remains unclear.

    Site-specific immune remodeling underlies resistance to dual immune checkpoint blockade in metastatic colorectal cancer · 2026 · DOI

  • The last decade has seen substantial advances, but much remains to be accomplished against a formidable foe.

    USFDA Oncology Drug Approvals from 2014- 2025: Comparing non-immunotherapy and immunotherapy approvals, their endpoints, and their efficacy. · 2026 · DOI

  • Although irAEs are well described clinically, there is limited evidence quantifying their downstream health care use and costs in Medicare beneficiaries with advanced NSCLC.

    Health care use and costs associated with clinically impactful immune-related adverse events during immune checkpoint inhibitor therapy for non–small cell lung cancer · 2026 · DOI

  • The clinical evidence is observational and cannot establish causation, - Reverse causation remains possible, - The mechanistic literature rests heavily on murine…

    Psychological distress as a host-state factor in cancer immunotherapy: clinical associations, neuroendocrine mechanisms, and future trial design · 2026 · DOI

  • Randomized trials to establish causation, - Studies to confirm the effect estimates, - Investigation of the ADRB1/ADRB2 question in human…

    Psychological distress as a host-state factor in cancer immunotherapy: clinical associations, neuroendocrine mechanisms, and future trial design · 2026 · DOI

  • PD-L1 IHC scoring by pathologists has limited predictive power, - The study only used two clinical trials, - The study only used non-small cell lung cancer patients, - The study did not investigate other types…

    Automated measurement of CD8+ T-cell distribution at the tumor epithelial–stromal interface is associated with NSCLC immunotherapy benefit and transcriptomic pathways · 2026 · DOI

  • Investigate the use of DACTI in other types of cancer, - Develop alternative biomarkers that overcome the limitations of PD-L1 IHC scoring, - Investigate the molecular underpinning of the atezolizumab-benefiter…

    Automated measurement of CD8+ T-cell distribution at the tumor epithelial–stromal interface is associated with NSCLC immunotherapy benefit and transcriptomic pathways · 2026 · DOI

  • Further well-controlled trials are needed to establish treatment guidelines, - Research on optimized patient selection is needed, - Studies on the use of PD-1 inhibitors in HIV-associated malignancies with larger sample sizes…

    Safety and Efficacy of Immune Checkpoint Inhibitors in Human Immunodeficiency Virus-Associated Cancer: A Systematic Scoping Review · 2025 · DOI

  • The paper identifies a gap in the literature regarding the coexistence of radiation recall pneumonitis, opportunistic infection, and electrolyte imbalance. The paper highlights the importance of differential diagnosis and close monitoring of electrolytes in NSCLC patients.

    Radiation Recall Pneumonitis with Pneumocystis jirovecii Superinfection and Treatment Induced Hyponatremia in a Patient with Non-Small-Cell Lung Cancer · 2025 · DOI

  • Further research is needed to identify new targets for tailored therapies and biomarkers to predict treatment responses, - The use of AI to predict patient responsiveness to immunotherapeutic agents should be explored, - In-depth cancer-type analysis is required to understand the complex mechanism behind response or resistance to ICI…

    Immunotherapy and Cancer: The Multi-Omics Perspective · 2024 · DOI

Most-cited papers in Cancer Immunotherapy and Biomarkers

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Open questions raised by papers listed on this page include: (1) Further studies are needed to validate the prognostic value of LIPI in patients with advanced NSCLC (“Prognostic Value of the Lung Immune Prognostic Index in Advanced Non-Small Cell…”, 2026); (2) The clinical relevance of Spark-like T cells in non-small cell lung cancer is not well understood (“Spark-like T cell represents a novel functional state of CD8+T cells associated…”, 2026); (3) Neutrophil-associated inflammation is associated with poor outcomes in hepatocellular carcinoma (HCC), but tumour-intrinsic regulators of neutrophil recruitment and checkpoint response remain unclear (“Novel retinoic acid receptor-related orphan receptor gamma inverse agonist…”, 2026); (4) ICOS, an inducible co-stimulatory receptor enriched on activated regulatory T cells (Tregs), represents a potential route of such immune regulation, but its role in breast cancer immunotherapy remains unclear (“ICOS blockade alleviates immune suppression in breast tumor microenvironment”, 2026); (5) Whether this reflects a failure to activate antitumor immunity or a failure to direct it remains unclear (“Site-specific immune remodeling underlies resistance to dual immune checkpoint…”, 2026). 2,273 gap statements have been mined from Cancer Immunotherapy and Biomarkers papers in our 7.9M-paper local library, which holds 9,870 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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