Systemic CD4 Immunity and PD-L1/PD-1 Blockade Immunotherapy

Escors, David; Bocanegra, Ana; Chocarro, Luisa; Blanco, Ester; Piñeiro‐Hermida, Sergio; Garnica, Maider; Fernández-Rubio, Leticia; Vera, Ruth; Arasanz, Hugo; Kochan, Grazyna

doi:10.3390/ijms232113241

Cited by 10 publications

(10 citation statements)

References 197 publications

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“…However, we have detected that CD4 + expression correlate with PD-L1 expression on immune cells and this could be a sign of a T cells-exhaustion [57]. It seems that exhausted T cells are not the aim of anti-PD-L1/PD-1 treatment [51].…”

Section: Discussionmentioning

confidence: 79%

“…It is very important mainly when we take into consideration that almost 10% had diagnosed muscle-invasive disease (MIBC) during the rst recurrence. The unfavorable outcome in this group of NMIBC patients might be associated with TIL dysfunction caused by the lack of CD4 + cells in the tumor microenvironment, which play a key role in antitumor immunity [51]. This small frequency could be connected with some kind of poorly immunogenic cancer cell variants, while in the same tissue samples an immune in ltration was generally not large and only an abundance of CD20 + cells in ltration was found.…”

Section: Discussionmentioning

confidence: 81%

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CD4, CD20 and PD-L1 as a marker of recurrence in non-muscle invasive bladder cancer

Semeniuk-Wojtaś

Modzelewska

Poddębniak-Strama³

et al. 2023

Preprint

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Introduction A tumor microenvironment plays an important role in bladder cancer development as well as in a treatment response. Purpose The aim of the study is to assess how the components of the microenvironment, in terms of cells, potentially affect tumor recurrence as well as to find the potential biomarkers for immunotherapy in NMIBC. Methods The study group consisted of 55 patients with primary NMIBC. Immunohistochemistry was performed on sections of primary papillary urothelial carcinoma of the bladder removed during transurethral resection of the tumor. Cox proportional hazard multiple regression analysis was performed to characterize tumors with the highest probability of an unfavorable outcome. Results The expression of analyzed variables was found in 90% of the examined tissues. Multivariate analysis confirmed that the CD4 (HR 1.19, 95% CI 1.07-1.32, p = 0.001), CD20 (HR 0.9, 95% CI 0.84-0.97, p = 0.008) and PD-L1 expressed on tumor cells (HR 0.05, 95% CI 0.008-0.29, p = 0.01) were independently associated with the risk of recurrence of bladder cancer. Patients with weak CD4+ cells (< 4,6%) infiltration and severe CD20+ infiltration (>10%) belong to the group with a lower risk of recurrence. The cancer in this group frequently recurs also after 12 months (p=0.0005). Conclusions The evaluation of CD4+ and CD20+ cells in the tumor microenvironment, in addition to PD-L1 on tumor cells, facilitates determination of a group of patients with a low risk of the recurrence that could also be recognized after 12 months following the primary tumor resection.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 81%

CD4, CD20 and PD-L1 as a marker of recurrence in non-muscle invasive bladder cancer

Semeniuk-Wojtaś

Modzelewska

Poddębniak-Strama³

et al. 2023

Preprint

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“…Tumor in ltration is usually regulated by T cells but also contains B cells, NK cells, DCs, macrophages, and neutrophils, which play an important role in the TME [41] . CD4 + T cells act as antitumor agents by regulating innate immunity, adaptive immunity, and immune detection [42] . In one study, T cell CD8 + subpopulation characteristics were identi ed by immunoassay as a prognostic marker for the recurrence of thyroid carcinoma [43] .…”

Section: Discussionmentioning

confidence: 99%

Effects of CCT subunits on clinical prognosis and tumor microenvironment in thyroid cancer

Bai,

Shi

2024

Preprint

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To investigate the expression, clinical significance, mechanism of action, and tumor microenvironment (TME) of eight subunits of the chaperonin-containing TCP1 complex (CCT/TRiC) in thyroid cancer (TC). Methods:The Cancer Genome Atlas (TCGA) and high-throughput functional genome (GEO) databases were used to analyze the differential expression of each CCT subunit in TC and normal tissues, and TCGA and Gene Expression Profiling Interaction Analysis (GEPIA) were used to analyze the effects of the expression levels of each CCT subunit on patient prognosis and the construction of survival risk models. Gene Enrichment Analysis (GSEA) was used to analyze the CCT of each subunit's biological functions, and the effects of each CCT subunit on the TC tumor microenvironment, drug sensitivity, and immune checkpoints were analyzed using TCGA and TCGA Tumor Immune Infiltration Analysis Database (TIMER2.0). Further analysis was performed to analyze the correlation between the expression of each CCT subunit and immune cell infiltration of TCs and drug targets. Results:There was a significant difference was found in the expression of each CCT subunit between the TC and normal thyroid tissues (P < 0.05). The subunits of CCT affect the prognosis of TC and are closely related to the TME, immune cell infiltration, immune checkpoints, and drug sensitivity. Conclusions:CCT complexes are potential molecular biomarkers for thyroid cancer, which may promote thyroid cancer development by affecting the tumor microenvironment, thus influencing patient prognosis. They also have the potential to serve as targets for diagnosis and immunotherapy of refractory thyroid cancer.

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“…Tumor-infiltrating lymphocytes (TILs) are an important part of the TME and are related to the metabolism of tumor cells and the local immune response. The number of T lymphocyte subsets is considered to be not only closely related to the metastasis, progression, and growth of malignant tumors, but also related to immune dysfunction, a key factor affecting the effect of tumor immunotherapy [7][8][9]. T lymphocytes are mainly divided into different functional subsets: CD4 + T cells, effector (CD8 + ) T cells, and other types of cells such as natural killer T (NKT) cells.…”

Section: Introductionmentioning

confidence: 99%

Association between radiomics features of DCE-MRI and CD8+ and CD4+ TILs in advanced gastric cancer

Huang¹,

Li²,

Xia³

et al. 2023

Pathol. Oncol. Res.

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Objective: The aim of this investigation was to explore the correlation between the levels of tumor-infiltrating CD8+ and CD4+ T cells and the quantitative pharmacokinetic parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced gastric cancer.Methods: We retrospectively analyzed the data of 103 patients with histopathologically confirmed advanced gastric cancer (AGC). Three pharmacokinetic parameters, Kep, Ktrans, and Ve, and their radiomics characteristics were obtained by Omni Kinetics software. Immunohistochemical staining was used to determine CD4+ and CD8+ TILs. Statistical analysis was subsequently performed to assess the correlation between radiomics characteristics and CD4+ and CD8+ TIL density.Results: All patients included in this study were finally divided into either a CD8+ TILs low-density group (n = 51) (CD8+ TILs < 138) or a high-density group (n = 52) (CD8+ TILs ≥ 138), and a CD4+ TILs low-density group (n = 51) (CD4+ TILs < 87) or a high-density group (n = 52) (CD4+ TILs ≥ 87). ClusterShade and Skewness based on Kep and Skewness based on Ktrans both showed moderate negative correlation with CD8+ TIL levels (r = 0.630–0.349, p < 0.001), with ClusterShade based on Kep having the highest negative correlation (r = −0.630, p < 0.001). Inertia-based Kep showed a moderate positive correlation with the CD4+ TIL level (r = 0.549, p < 0.001), and the Correlation based on Kep showed a moderate negative correlation with the CD4+ TIL level, which also had the highest correlation coefficient (r = −0.616, p < 0.001). The diagnostic efficacy of the above features was assessed by ROC curves. For CD8+ TILs, ClusterShade of Kep had the highest mean area under the curve (AUC) (0.863). For CD4+ TILs, the Correlation of Kep had the highest mean AUC (0.856).Conclusion: The radiomics features of DCE-MRI are associated with the expression of tumor-infiltrating CD8+ and CD4+ T cells in AGC, which have the potential to noninvasively evaluate the expression of CD8+ and CD4+ TILs in AGC patients.

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Systemic CD4 Immunity and PD-L1/PD-1 Blockade Immunotherapy

Cited by 10 publications

References 197 publications

CD4, CD20 and PD-L1 as a marker of recurrence in non-muscle invasive bladder cancer

CD4, CD20 and PD-L1 as a marker of recurrence in non-muscle invasive bladder cancer

Effects of CCT subunits on clinical prognosis and tumor microenvironment in thyroid cancer

Association between radiomics features of DCE-MRI and CD8+ and CD4+ TILs in advanced gastric cancer

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