Cancer Immunology Reserch

Endogenous CD4 T cells that recognize ALK and the NPM1::ALK fusion protein can be expanded from human peripheral blood

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Cancer Immunol Res. 2025 Jan 7. doi: 10.1158/2326-6066.CIR-24-0445. Online ahead of print. ABSTRACT Anaplastic lymphoma kinase (ALK)-fusion proteins resulting from chromosomal rearrangements are promising targets for cancer immunotherapy. While ALK-specific CD8+ T cells and epitopes presented on MHC class I have been identified in patients with ALK-positive malignancies, little is known about ALK-specific CD4+ T … Read more

The spatial organization of cDC1 with CD8+ T cells is critical for the response to immune checkpoint inhibitors in melanoma patients

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Cancer Immunol Res. 2025 Jan 7. doi: 10.1158/2326-6066.CIR-24-0421. Online ahead of print. ABSTRACT Dendritic cells (DCs) are promising targets for cancer immunotherapies because of their central role in the initiation and control of immune responses. The rare cDC1 population is of particular interest because of its remarkable ability to cross-present antigens (Ag) to CD8+ T … Read more

NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control

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Cancer Immunol Res. 2025 Jan 6:OF1-OF19. doi: 10.1158/2326-6066.CIR-24-0298. Online ahead of print. ABSTRACT Despite advances in cancer immunotherapy, such as targeting the PD-1/PD-L1 axis, a substantial number of patients harbor tumors that are resistant or relapse. Selective engagement of T-cell co-stimulatory molecules with bispecific antibodies may offer novel therapeutic options by enhancing signal 1-driven activation … Read more

Spatial Organization of Macrophages in CTL Rich Hepatocellular Carcinoma Influences CTL Antitumor Activity

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Cancer Immunol Res. 2025 Jan 2. doi: 10.1158/2326-6066.CIR-24-0589. Online ahead of print. ABSTRACT Despite the pivotal role of cytotoxic T lymphocytes (CTLs) in anti-tumor immunity, a substantial proportion of CTL-rich hepatocellular carcinoma (HCC) patients experience early relapse or immunotherapy resistance. However, spatial immune variations impacting the heterogeneous clinical outcomes of CTL-rich HCCs remain poorly understood. … Read more

Lung cancer-intrinsic SOX2 expression mediates resistance to checkpoint blockade therapy by inducing Treg cell-dependent CD8+ T-cell exclusion

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Cancer Immunol Res. 2025 Jan 2. doi: 10.1158/2326-6066.CIR-24-0184. Online ahead of print. ABSTRACT Tumor cell-intrinsic signaling pathways can drastically affect the tumor immune microenvironment, promoting tumor progression and resistance to immunotherapy by excluding immune-cell populations from the tumor. Several tumor cell-intrinsic pathways have been reported to modulate myeloid-cell and T-cell infiltration creating “cold” tumors. However, … Read more

Profiling Multiple CD8+ T-Cell Functional Dimensions Enhances Breast Cancer Immune Assessment

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Cancer Immunol Res. 2024 Dec 23. doi: 10.1158/2326-6066.CIR-24-0235. Online ahead of print. ABSTRACT CD8+ T-cell abundance is insufficient to assess antitumor immunity and shows poor performance in predicting breast cancer prognosis and immunotherapy response, presumably owing to the complexity of CD8+ T-cell functionalities. While single-cell RNA sequencing (scRNA-seq) can dissect the multifaceted functions of CD8+ … Read more

Mathematical modeling predicts optimal immune checkpoint inhibitor and radiotherapy combinations and timing of administration

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Cancer Immunol Res. 2024 Dec 12. doi: 10.1158/2326-6066.CIR-24-0610. Online ahead of print. ABSTRACT Radiotherapy (RT) combined with immune checkpoint inhibitor (ICI) therapy has attracted substantial attention due to its potential to improve outcomes for patients with several types of cancer. However, the optimal administration timepoints and drug combinations remain unclear because the mechanisms underlying RT-induced … Read more

The FcγRIIIA (CD16) L48-H/R polymorphism enhances NK cell-mediated antibody-dependent cellular cytotoxicity by promoting serial killing

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Cancer Immunol Res. 2024 Dec 12. doi: 10.1158/2326-6066.CIR-24-0384. Online ahead of print. ABSTRACT Many tumor-specific monoclonal antibody therapies stimulate antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells through FcγRIIIa (CD16). The efficacy of these ADCC-based immunotherapies is potentiated in patients with the common CD16 polymorphic variant F158-V that increases the binding affinity between the … Read more

The C5a/C5aR1 axis promotes migration of tolerogenic dendritic cells to lymph nodes, impairing the anticancer immune response

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Cancer Immunol Res. 2024 Dec 12. doi: 10.1158/2326-6066.CIR-24-0250. Online ahead of print. ABSTRACT The precise mechanisms by which the complement system contributes to the establishment of an immunosuppressive tumor microenvironment (TME) and promotes tumor progression remain unclear. In this study, we investigated the expression and function of complement C5a receptor 1 (C5aR1) in human and … Read more

Tertiary lymphoid structures in pancreatic cancer are structurally homologous, share gene expression patterns and B-cell clones with secondary lymphoid organs but show increased T-cell activation

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Cancer Immunol Res. 2024 Dec 11. doi: 10.1158/2326-6066.CIR-24-0299. Online ahead of print. ABSTRACT Tertiary lymphoid structures (TLS) in cancer are considered ectopic hotspots for immune activation that are similar to lymphoid follicles in secondary lymphoid organs (SLO). This study elucidates shared and TLS/SLO-specific features in pancreatic ductal adenocarcinoma (PDAC). TLS abundance was related to superior … Read more

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