Cancer Immunotherapy Research Articles

1333P Prognostic value of circulating nucleosomes during treatment with or without immunotherapy in non-small lung cancer (NSCLC): Results from the NUCLEO-lung study

1333P Prognostic value of circulating nucleosomes during treatment with or without immunotherapy in non-small lung cancer (NSCLC): Results from the NUCLEO-lung study

132P The potential of VEGF-A in the peripheral blood serum as a biomarker of response in the addition of bevacizumab with chemotherapy-combined immunotherapy for metastatic nonsquamous non-small cell lung cancer

132P The potential of VEGF-A in the peripheral blood serum as a biomarker of response in the addition of bevacizumab with chemotherapy-combined immunotherapy for metastatic nonsquamous non-small cell lung cancer

2012P Role of first-line immunotherapy in urothelial cancer with bone metastases: A national cancer database analysis of 3971 patients

2012P Role of first-line immunotherapy in urothelial cancer with bone metastases: A national cancer database analysis of 3971 patients

1055P Analysis of correlation between quality of life (QoL) results and survival outcomes in phase III clinical trials testing immunotherapy in metastatic cancers

1055P Analysis of correlation between quality of life (QoL) results and survival outcomes in phase III clinical trials testing immunotherapy in metastatic cancers

262P Predictive clinico-biological factors of toxicity associated to neo-adjuvant chemo- immunotherapy in early-stage triple-negative breast cancer

262P Predictive clinico-biological factors of toxicity associated to neo-adjuvant chemo- immunotherapy in early-stage triple-negative breast cancer

Recent advances in immunotherapy for pancreatic cancer: a narrative review

Recent advances in immunotherapy for pancreatic cancer: a narrative review

402P Inflammatory biomarkers for predicting the efficacy of immunotherapy in advanced breast cancer

402P Inflammatory biomarkers for predicting the efficacy of immunotherapy in advanced breast cancer

12P STING-activable pyroptotic nanoparticles deliver GSDMDNT mRNA for in situ pancreatic cancer vaccination and immunotherapy

12P STING-activable pyroptotic nanoparticles deliver GSDMDNT mRNA for in situ pancreatic cancer vaccination and immunotherapy

Mucosal-associated invariant T cells modulate innate immune cells and inhibit colon cancer growth.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions and have potentials for use as adoptive cell therapy. However, studies into their anti-cancer activity, including their role in colon cancer, are limited. Using an animal model of colon cancer, we showed that peritumoral injection of invivo-expanded MAIT cells into RAG1-/- mice with MC38-derived tumours inhibits tumour growth compared to control. Multiplex cytokine analyses showed that tumours from the MAIT cell-treated group have higher expression of markers for eosinophil-activating cytokines, suggesting a potential association between eosinophil recruitment and tumour inhibition. In a human peripheral leukocyte co-culture model, we showed that leukocytes stimulated with MAIT ligand showed an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. In conclusion, we showed that MAIT cells have a protective role in a murine colon cancer model, associated with modulation of the immune response to cancer, potentially involving eosinophil-associated mechanisms. Our results highlight the potential of MAIT cells for non-donor restricted colon cancer immunotherapy.

Frontispiece: A NIR‐Light‐Activated and Lysosomal‐Targeted Pt(II) Metallacycle for Highly Potent Evoking of Immunogenic Cell Death that Potentiates Cancer Immunotherapy of Deep‐Seated Tumors

Frontispiece: A NIR‐Light‐Activated and Lysosomal‐Targeted Pt(II) Metallacycle for Highly Potent Evoking of Immunogenic Cell Death that Potentiates Cancer Immunotherapy of Deep‐Seated Tumors

A thermoresponsive metabolic nanomodulator for achieving photochemotherapy-sensitized cancer immunotherapy

The largest obstacle that impedes the successful clinical use of anticancer nanodrugs lies in their unsatisfactory therapeutic performance even if multiple drug treatments are applied, which may cause tumor relapse and drug resistance. Therefore, it is challenging to develop effective nanodrugs that can eradicate tumors with only single injection. Herein, we construct a metabolic nanomodulator (denoted as ISM liposome), where the phototherapeutic dye IR825-NH2, the chemodrug shikonin, and the mitochondrial respiration inhibitor metformin are encapsulated, to closely synergize phototherapy, chemotherapy, and immunotherapy via the laser-triggered on-demand metabolism regulation for realizing robust anticancer potency after only single injection and irradiation. Upon near-infrared laser irradiation, IR825-NH2 can generate reactive oxygen species and mild heat to enable the phototherapeutic cytotoxcity and thermoresponsive release of the loaded drugs. Then, cellular oxygen can be spared by the released metformin via metabolic modulation and be utilized by shikonin to further amplify the oxidative stress in cancer cells. More importantly, the ISM liposome-mediated photochemotherapy can subsequently elicit a strong immunogenic cell death (ICD) effect and sensitize the immunosupressive tumor to the ICD-induced immunotherapy, thereby achieving strong tumor inhibition and even eradication. The metabolic nanomodulator-based photochemotherapy-sensitized cancer immunotherapy may represent a new solution to fight against cancer.

158P Patterns of immune-related adverse events in early-phase cancer immunotherapy trials

158P Patterns of immune-related adverse events in early-phase cancer immunotherapy trials

1039P Discovery of a novel inhibitor of PD-L1 maturation that overcomes adaptive resistance to cancer immunotherapy

1039P Discovery of a novel inhibitor of PD-L1 maturation that overcomes adaptive resistance to cancer immunotherapy

Unveiling the functional roles of patient-derived tumour organoids in assessing the tumour microenvironment and immunotherapy.

Recent studies have established the pivotal roles of patient-derived tumour organoids (PDTOs), innovative three-dimensional (3D) culture systems, in various biological and medical applications. PDTOs, as promising tools, have been established and extensively used for drug screening, prediction of immune response and assessment of immunotherapeutic effectiveness in various cancer types, including glioma, ovarian cancer and so on. The overarching goal is to facilitate the translation of new therapeutic modalities to guide personalised immunotherapy. Notably, there has been a recent surge of interest in the co-culture of PDTOs with immune cells to investigate the dynamic interactions between tumour cells and immune microenvironment. A comprehensive and in-depth investigation is necessary to enhance our understanding of PDTOs as promising testing platforms for cancer immunotherapy. This review mainly focuses on the latest updates on the applications and challenges of PDTO-based methods in anti-cancer immune responses. We strive to provide a comprehensive understanding of the potential and prospects of PDTO-based technologies as next-generation strategies for advancing immunotherapy approaches.

An improved approach to generate IL-15+/+/TGFβR2−/− iPSC-derived natural killer cells using TALEN

We present a TALEN-based workflow to generate and maintain dual-edited (IL-15+/+/TGFβR2-/-) iPSCs that produce enhanced iPSC-derived natural killer (iNK) cells for cancer immunotherapy. It involves using a cell lineage promoter for knocking in (KI) gene(s) to minimize the potential effects of expression of any exogenous genes on iPSCs. As a proof-of-principle, we KI IL-15 under the endogenous B2M promoter and show that it results in high expression of the sIL-15 in iNK cells but minimal expression in iPSCs. Furthermore, given that it is known that knockout (KO) of TGFβR2 in immune cells can enhance resistance to the suppressive TGF-β signaling in the tumor microenvironment, we develop a customized medium containing Nodal that can maintain the pluripotency of iPSCs with TGFβR2 KO, enabling banking of these iPSC clones. Ultimately, we show that the dual-edited IL-15+/+/TGFβR2-/- iPSCs can be efficiently differentiated into NK cells that show enhanced autonomous growth and are resistant to the suppressive TGF-β signaling.

Design, synthesis and structure-activity relationship of malonic acid non-nucleoside derivatives as potent CD73 inhibitors

High levels of extracellular adenosine in tumor microenvironment (TME) has extensive immunosuppressive effect. CD73 catalyzes the conversion of AMP into adenosine and regulates its production. Inhibiting CD73 can reduce the level of adenosine and reverse adenosine-mediated immune suppression. Therefore, CD73 has emerged as a valuable target for cancer immunotherapy. Here, a new series of malonic acid non-nucleoside derivatives were designed, synthesized and evaluated as CD73 inhibitors. Among them, compounds 18 and 19 exhibited significant inhibition activities against hCD73 with IC50 values of 0.28 μM and 0.10 μM, respectively, suggesting the feasibility of replacing the benzotriazole moiety in the lead compound. This study explored the novelty and structural diversity of CD73 inhibitors.

Frontispiz: A NIR‐Light‐Activated and Lysosomal‐Targeted Pt(II) Metallacycle for Highly Potent Evoking of Immunogenic Cell Death that Potentiates Cancer Immunotherapy of Deep‐Seated Tumors

Frontispiz: A NIR‐Light‐Activated and Lysosomal‐Targeted Pt(II) Metallacycle for Highly Potent Evoking of Immunogenic Cell Death that Potentiates Cancer Immunotherapy of Deep‐Seated Tumors

Voluntary exercise sensitizes cancer immunotherapy via the collagen inhibition-orchestrated inflammatory tumor immune microenvironment

Physical activity reduces cancer-associated mortality through multiple mechanisms, including tumor immune microenvironment (TIME) reprogramming. However, whether and how physiological interventions promote anti-tumor immunity remain elusive. Here, we report that clinically relevant voluntary exercise promotes muscle-derived extracellular vesicle (EV)-associated miR-29a-3p for tumor extracellular matrix (ECM) inhibition in patients and mouse models, thereby permitting immune cell infiltration and immunotherapy. Mechanistically, an unbiased screening identifies EV-associated miR-29a-3p in response to leisure-time physical activity or voluntary exercise. MiR-29a-3p-containing EVs accumulate in tumors and downregulate collagen composition by targeting COL1A1. Gain- and loss-of-function experiments and cytometry by time of flight (CyTOF) demonstrate that myocyte-secreted miR-29a-3p promotes anti-tumor immunity. Combining immunotherapy with voluntary exercise or miR-29a-3p further enhances anti-tumor efficacy. Clinically, miR-29a-3p correlates with reduced ECM, increased Tcell infiltration, and response to immunotherapy. Our work reveals the predictive value of miR-29a-3p for immunotherapy, provides mechanistic insights into exercise-induced anti-cancer immunity, and highlights the potential of voluntary exercise in sensitizing immunotherapy.

Amplifying STING activation and immunogenic cell death by metal-polyphenol coordinated nanomedicines for enhanced cancer immunotherapy

Amplifying STING activation and immunogenic cell death by metal-polyphenol coordinated nanomedicines for enhanced cancer immunotherapy

Analysis of Spermine Oxidase gene and proinflammatory cytokines expression in gastric cancer patients with and without Helicobacter pylori infection – a pilot study in Polish population

PurposeMany types of cancer have infectious origins. Gastric cancer patients can demonstrate high seroprevalence of Helicobacter pylori (H. pylori). The aim of the present study was to assess the expression of SMOX gene in the group of Polish patients with gastric cancer. SMOX is believed to promote H. pylori-induced carcinogenesis via inflammation, DNA damage and activation of β-catenin signaling. We also assessed the mRNA expression of selected pro-inflammatory cytokines, i.e. IL-2, IFN-γ, TNF-α, and antimicrobial peptide, cathelicidin. Materials/methodsThe study material consisted of gastric tissue samples collected during total gastrectomy from three different places in stomach: from primary tumor, 3cm away from the primary lesion, and from the wall opposite to the primary tumor. After RNA isolation, qPCR reactions were performed for the relevant genes. ResultsThe obtained results confirmed an increased level of SMOX expression in gastric cancer patients with the history of H. pylori infection. And, as far as we know, this is the first study on SMOX gene expression conducted on tissue taken from a patient, not on a cell line. The levels of pro-inflammatory cytokines, i.e. IL-2, IFN-γ, TNF-α, were also increased, thus indicating their contribution to the specific inflammatory microenvironment of the tumor. Interestingly, the levels of CAMP, encoding antimicrobial peptide, were reduced in all tissue types. ConclusionsThe findings confirm that SMOX plays a role in gastric carcinogenesis. However, further research is needed on the role of inflammatory and other factors involved in this process to identify targets for cancer immunotherapy.