Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy

Khelil, Myriam Ben; Godet, Yann; Abdeljaoued, Syrine; Borg, Christophe; Adotévi, Olivier; Loyon, Romain

doi:10.3390/cancers14010260

Cited by 36 publications

(30 citation statements)

References 245 publications

(283 reference statements)

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“…An explanation may be related to functional impairment of CD4 T cells, regardless of their circulating levels. Indeed, chronic inflammation and the accumulation of immunosuppressive factors at the metastatic stage can lead to functional alterations in CD4 T lymphocytes, which play a crucial role in the immune surveillance of cancers [ 24 – 26 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of CD4+ T lymphopenia in non-small cell lung Cancer

et al. 2022

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Background There is a paucity of data regarding the prognostic influence of peripheral blood CD4+ T lymphopenia in non-small cell lung cancer (NSCLC). Therefore, we investigated the prognostic value of T lymphopenia in NSCLC. Materials Treatment-naive patients with a pathological diagnosis of NSCLC, at clinical stage I to IV were included in the prospective TELOCAP1 study. Lymphocytes count was evaluated in peripheral blood by flow cytometry. CD4+ and CD8+ T lymphopenia were defined as an absolute count of < 500/μL and < 224/μL respectively. The prognostic value of T lymphopenia was analyzed in the whole population, in local/loco-regional (stage I-IIIB) and in advanced (stage IV) NSCLC disease, using the Kaplan-Meier method and Cox regression models for survival curves and multivariate analysis, respectively. Results Between July 2010 and January 2014, 169 evaluable patients with clinical stage I to IV NSCLC were prospectively enrolled. The prevalence of CD4+ and CD8+ T lymphopenia was similar in the study population (around 29%). Patients with CD4+ T lymphopenia showed lower overall survival than those with CD4+ T lymphocytes count > 500/μL (median overall survival (OS) 16.1 versus 21.7 months, hazard ratio (HR): 1.616 [95% CI: 1.1–2.36], p = 0.012). This association with OS was especially marked in local/loco-regional NSCLC stages (median OS, 21.8 versus 72 months, respectively, HR: 1.88 [95% CI: 0.9–3.8], p = 0.035). Multivariate analysis confirmed the worse prognosis associated with CD4+ T lymphopenia in local/loco-regional NSCLC, but not in metastatic patients (HR 2.028 [95% CI = 1.065–3.817] p = 0.02). Restricted cubic spline analysis showed that patients with CD4+ T lymphocytes count ≤500/μL displayed a high risk of death regardless of NSCLC clinical stage. There was no obvious relationship between CD8+ T lymphopenia and clinical outcome. Conclusion We identified CD4+ T lymphopenia as an independent prognostic factor in local/loco-regional stages of NSCLC and CD4+ T lymphopenia is also associated with a high risk of death, regardless of NSCLC clinical stage. Trial registration EUDRACT: 2009-A00642–55.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of CD4+ T lymphopenia in non-small cell lung Cancer

et al. 2022

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“…And previous studies have proven that the immune cell infiltration features with a better prognosis were marked by high T cells in CRC patients ( Guo J.-N. et al, 2022 ; Lundberg et al, 2021 ; Zinovkin et al, 2021 ). CD4 + T cells are indispensable in orchestrating antitumor immunity ( Ben Khelil et al, 2022 ). Various subsets of CD4 + T cells play multifaceted roles in the cancer response, including Th2, and Th17 ( Galon and Bruni, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Necroptosis-Related Genes Associated With Immune Activity and Prognosis of Colorectal Cancer

Peng

Guo

et al. 2022

Front. Genet.

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This study aims at screening out the key necroptosis-related genes in colorectal cancer and elucidating the role of necroptosis-related genes in the immune activity and prognosis of colorectal cancer (CRC). The CRC patients’ data were downloaded from The Cancer Genome Atlas (TCGA). The non-negative matrix factorization method was applied to identify new molecular subgroups. Survival analysis and single sample Gene Set Enrichment Analysis were performed to determinate the differences in the overall survival time and immune status of the subgroups. Prognostic model was constructed on the basis of univariate Cox regression and LASSO analysis. Functional analyses were used to explore the potential mechanisms. Based on prognostic related necroptosis genes, we identify two molecular subgroups with significantly different survival. The better prognosis was associated with more active immune infiltration and upregulated expression of immune checkpoints. We screened nine necroptosis related genes as key prognostic genes and established a risk model, which showed a good potential for survival prediction in colorectal cancer. Nomogram assessment showed that the model had high reliability for predicting the prognosis of colorectal cancer patients. The high-risk and low-risk group also has different sensitivity to immunotherapy and commonly used drugs for colorectal cancer. Overall, necroptosis related genes were involved in the immune microenvironment of colorectal cancer patient, could be utilized to predict the prognosis of colorectal cancer and develop more individualized treatment.

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“…The high infiltration and activation of CD8 + T cells are positively associated with the prognosis of CRC, suppressing metastasis development of colorectal cancer (Camus et al, 2009;Bruni et al, 2020). D4+T cell subsets had a complicated influence on tumor progression, including Th2, Th17, Tfh and so on (Galon and Bruni, 2020;Ben Khelil et al, 2022). Th17 cells could enhance anti-tumor immunity by producing IL-17 to induce the polarization of M1 macrophage and recruiting anti-tumor immune cells, for example, NK and CD8 + T cells (Al Omar et al, 2013;Guéry and Hugues, 2015;Jang et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Amino acid metabolism genes associated with immunotherapy responses and clinical prognosis of colorectal cancer

Peng

Zheng

Guo

et al. 2022

Front. Mol. Biosci.

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Based on amino acid metabolism-related genes (AAMRGs), this study aimed at screening out key prognosis-related genes and finding the underlying correlation between the amino acid metabolism and tumor immune microenvironment of colorectal cancer. A total of 448 amino acid metabolism-related genes were obtained from MsigDB. The risk signature was built based on differential expression genes, univariate Cox, and LASSO analyses with 403 patients’ data downloaded from the TCGA database. Survival analysis and independence tests were performed to confirm the validity of the risk signature. Single-sample gene set enrichment analysis (ssGSEA), tumor mutation burden (TMB), the score of tumor immune dysfunction and exclusion (TIDE), the immunophenoscore obtained from The Cancer Immunome Atlas database, and the IC50 of drugs were used to find the relationship among the risk signature, immune status, immunotherapy response, and drug sensitivity of colorectal cancer. We identified five amino acid metabolism-related genes for the construction of the risk signature, including ENOPH1, ACAT1, ALDH4A1, FAS, and ASPG. The low-risk group was significantly associated with a better prognosis (p < 0.0001). In the entire set, the area under the curve (AUC) for 1, 3, and 5 years was 0.717, 0.734, and 0.764, respectively. We also discovered that the low-risk subgroup was related to more activity of immune cells, had higher expression of some immune checkpoints, and was more likely to benefit from immunotherapy. ssGSEA revealed that except the processes of glutamine histidine, lysine, tyrosine, and L-phenylalanine metabolism, the other amino acid metabolism pathways were more active in the samples with the low risk scores, whereas the activities of synthesis and transportation of most amino acids were similar. Hedgehog signaling, WNT/β-catenin signaling, mitotic, notch signaling, and TGF-β signaling were the top five pathways positively associated with the risk score. To sum up, AAMRGs were associated with the immune microenvironment of CRC patients and could be applied as biomarkers to predict the prognosis and immunotherapy response of patients.

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Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy

Cited by 36 publications

References 245 publications

Prognostic value of CD4+ T lymphopenia in non-small cell lung Cancer

Prognostic value of CD4+ T lymphopenia in non-small cell lung Cancer

Necroptosis-Related Genes Associated With Immune Activity and Prognosis of Colorectal Cancer

Amino acid metabolism genes associated with immunotherapy responses and clinical prognosis of colorectal cancer

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