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During the TIMO meeting 2023, national and international scientists as well as clinicians gave novel insights as well as perspectives into basic and translational tumor immunology. https://dgfi.org/arbeitskreise/ak-tumorimmunologie/meeting/ [ABSTRACT FROM AUTHOR]

During the TIMO meeting 2022, national and international scientists as well as clinicians gave novel insights as well as perspectives into basic and translational tumor immunology. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is a leading cause of cancer-related death worldwide. Ferroptosis, a form of cell death characterized by iron-dependent lipid peroxidation. However, the involvement of ferroptosis in the regulation of immune cell infiltration and its immunotherapeutic efficacy in LUAD remain unclear. Methods: The Cancer Genome Atlas (TCGA) LUAD cohort was used to assess the survival prognosis of FRGs and construct a seven-gene risk signature. Correlation tests, difference tests, and a cluster analysis were performed to explore the role of FRGs in the immune microenvironment and their immunotherapeutic efficacy in LUAD. The effects of FRGs on LUAD cells were assessed by Western blot, iron assay, and lipid peroxidation assay. Results: The seven-gene risk signatures of patients with LUAD were established and validated. FRG clustering based on 70 differentially expressed FRGs was associated with the immune microenvironment and indicated potential immune subtypes of LUAD. The seven-gene risk signature was an independent prognostic factor for LUAD and was used to divide the LUAD cohort into a high-risk and a low-risk group. Immunocyte infiltration levels, immune checkpoints, and immunotherapy response rates were significantly different between the two groups. Patients with high risk scores had lower overall levels of immunocyte infiltration but higher immunotherapy response rates. The key gene ribonucleotide reductase subunit M2 (RRM2) was associated with LUAD prognosis, which may be related to its ability to regulate the infiltration levels of activated mast cells and activated CD4 memory T cells. In addition, RRM2 was involved in ferroptosis, and its expression was up regulated in lung cancer tissues and the LUAD cell lines. Silencing RRM2 can inhibit the proliferation and induce ferroptosis of H1975 cells suggesting that silencing RRM2 could promote ferroptosis in H1975 cells. Conclusion: Our results revealed RRM2 as a promising biomarker and therapeutic target associated with tumor immune infiltration in patients with LUAD. [ABSTRACT FROM AUTHOR]

The integrated landscape of ferroptosis regulatory patterns and their association with colon microenvironment have been demonstrated in recent studies. However, the ferroptosis-related immunotherapeutic signature for colon cancer (CC) remains unclear. We comprehensively evaluated 1623 CC samples, identified patterns of ferroptosis modification based on ferroptosis-associated genes, and systematically correlated these patterns with tumor microenvironment (TME) cell infiltration characteristics. In addition, the ferroptosis-regulated gene score (FRG-score) was constructed to quantify the pattern of ferroptosis alterations in individual tumors. Three distinct patterns of ferroptosis modification were identified, including antioxidant defense, iron toxicity, and lipid peroxidation. The characteristics of TME cell infiltration under these three patterns were highly consistent with the three immune phenotypes of tumors, including immune-inflamed, immune-excluded and immune-desert phenotypes. We also demonstrated that evaluation of ferroptosis regulatory patterns within individual tumors can predict tumor inflammatory status, tumor subtype, TME stromal activity, genetic variation, and clinical outcome. Immunotherapy cohorts confirmed that patients with low FRG-scores showed remarkable therapeutic and clinical benefits. Furthermore, the hub gene apolipoprotein L6 (APOL6), a drug-sensitive target associated with cancer cell ferroptosis, was identified through our proposed novel key gene screening process and validated in CC cell lines and scRNA-seq. • This work investigated the integrated landscape of ferroptosis regulation patterns and their association with TME. • The characteristics of TME cell infiltration under identified three patterns were in accord well with three immune phenotypes of tumors. • FRG-score quantified ferroptosis modification patterns and predicted clinical response to immunotherapy and prognosis well. • The procedures for screening key genes were developed and APOL6 was preliminarily identified as a promising target in CC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Genetic and transcriptional changes in of FRGs in gastric cancer. • Multilayer FRGs changes correlate with patients clinicopathology, prognosis, and TME cell infiltration. • Low FRG-score, due to its MSI-H, high mutational load and immune activation, indicates the possible advantage of OS. • The FRG-score was closely related to the cancer stem cell (CSC) index and the sensitive degree of chemotherapeutic drug. Ferroptosis is a distinct form of cell death characterized by unique morphology, biochemistry, and genetics, playing a crucial role in the initiation, progression, prognosis, and therapeutic strategies of tumors. However, the impact of ferroptosis-related genes (FRGs) on the tumor microenvironment (TME) remains unclear. This study may advance the existing knowledge of FRGs in gastric cancer, and push ahead with more effective prognostic assessment and the development of more effective immunotherapy approaches. FRGs were acquired from the FerrDb database and a consensus clustering technique was adopted to categorize patients with GC into groups in line with the expression profiles of 44 FRGs in order to further investigate the expression properties of these proteins. Assessment of the immune status, microsatellite instability (MSI) and cancer stem cell (CSC) index between the high- and low- risk groups to assess the proportion of TIICs in the TME, ssGSVA was adopted to detect the abundance of infiltrating immune cells from the low-risk and high-risk groups. Expression levels of eight ferroptosis-related genes of prognostic signature in GC tissues and adjacent normal tissues was detected by RT-PCR. In the GC cohort, TP53 has the highest mutation frequency (44 %), and was shown to be highly linked with the expression levels of 11 FRGs. In accordance with the Kaplan-Meier curve, the overall survival time of patients with subtype A (Low FRG-score) discernibly exceeded that of patients with subtype B (High FRG-score).In addition, there is a significant difference in the infiltration of most immune cells between subtype A and subtype B, and some important immune checkpoints (CTLA4, PDCD1, CD274, LAG3, PDCD1LG2, and HAVCR2) have higher expression in cluster A. Finally, low FRG-scores were significantly associated with MSI-H status, while high FRG-scores were significantly associated with microsatellite stable status (MSS). FRG-score is negatively related to the cancer stem cell (CSC). Low FRG-score, due to its high microsatellite instability (MSI-H), high mutational load and immune activation, indicates the possible advantage of OS. In addition, the FRG-score was closely related to the cancer stem cell (CSC) index and the sensitive degree of chemotherapeutic drug. [ABSTRACT FROM AUTHOR]