Prognostic value of immunological profile based on CD8+ and FoxP3+ T lymphocytes in the peritumoral and intratumoral subsites for renal cell carcinoma

Teke, Kerem; Bayrak, Büşra Yaprak; Yuksekkaya, Mustafa; Uslubaş, Ali Kemal; Kosem, Mehmet Esat; Yılmaz, Hasan; Kara, Önder; Dillioğlugil, Özdal

doi:10.1007/s11255-020-02592-x

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…Studies have confirmed that the composition and spatial distribution of immune cells in the tumor microenvironment (TME) greatly influence the efficacy of immunotherapy and patient outcomes ( 7 – 11 ). For example, patients with considerable infiltration of immune cells in tumors, especially CD8 + T cells, helper T cells (CD4 + ), and macrophages, would benefit most from the immunotherapy ( 12 , 13 ). However, the spatial distribution profiles of immune cells in the pMMR CRC immune microenvironment and the relationships with clinical prognosis have not been clearly established, which warrants further investigation.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Immune Landscape Reveals Prognostic Significance of Cytotoxic CD4+ T Cells in the Central Region of pMMR CRC

Liu

Yan

et al. 2021

Front. Oncol.

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BackgroundMismatch repair proficient colorectal cancer (pMMR CRC) lacks effective treatments and has a poor prognosis, which can be attributed to the complexity of tumor microenvironment. The coordinated function of immune cells is vital to anti-tumor immunity. However, the spatial characteristics of immune cells in the pMMR CRC immune microenvironment and their relationship with clinical prognosis are not fully understood. Meanwhile, the immune modulatory effect of neoadjuvant chemotherapy (NCT), which is the first-line treatment of pMMR CRC, needs further investigation. Therefore, this study aims to explore the spatial dynamics of immune cells and its prognostic value in pMMR CRC.MethodsWe analyzed the various immune cells in formalin-fixed, paraffin-embedded tumor tissues which were collected from 77 patients with stage II/III of pMMR CRC, including 39 non-NCT treated and 38 NCT treated patients. We used the optimized multiplex immunohistochemistry (mIHC) to identify and quantify the density, type and location of immune cells in pMMR CRC. Multivariate survival analysis was performed to assess the relationship of immune profiles and clinical prognosis of pMMR CRC patients.ResultsThe densities of most T cell subsets, B cells and macrophages were higher in the central region of the pMMR CRC than in the invasion margin. Tumor infiltrating lymphocytes (TILs), especially the infiltration of CD4+ GzmB+ T cells in the central region of the tumor was identified to be positively correlated with the prognosis of the patients. Multivariate analysis confirmed that CD4+ GzmB+ T cells population was an independent predictor of disease-free survival (DFS) in non-NCT group. Meanwhile, NCT enhanced the infiltration of CD4+ GzmB+ T cells in the central region of the pMMR CRC, which was also identified as an independent protective factor of overall survival (OS) and DFS in NCT group.ConclusionWe demonstrated that the level of CD4+ GzmB+ T cells located in the center of tumor could provide great prognostic value for pMMR CRC patients. And the application of neoadjuvant chemotherapy further improves the infiltration of CD4+ GzmB+ T cells in the central compartment. Further studies into the application of CD4+ GzmB+ T cells in tumor immunotherapy are needed.

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Section: Introductionmentioning

confidence: 99%

Analysis of Immune Landscape Reveals Prognostic Significance of Cytotoxic CD4+ T Cells in the Central Region of pMMR CRC

Liu

Yan

et al. 2021

Front. Oncol.

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“…At least five randomly selected sections were scored for histological healing by a numerical scoring system of 1 to 10 points [ 24 ]. Inflammation was evaluated according to the lymphocyte infiltration by a scoring system; 0 for no inflammation, 1 for mild inflammation, 2 for moderate inflammation, and 3 for severe inflammation [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Effects of Linagliptin and Pioglitazone on Fracture Healing in an Experimental Type 2 Diabetes Rat Model

Mraja¹,

Çağlar²,

Uslu³

et al. 2022

Cureus

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Aim: Our study aimed to examine the effects of Linagliptin, Pioglitazone, and their combination on fracture healing in a diabetes rat femur fracture model. Material and methods: Type 2 diabetes mellitus (T2DM) induced rats were randomly divided into four groups: non-treated diabetes group (TD), Pioglitazone group (P), Linagliptin group (L), and Pioglitazone and Linagliptin group (PL). Daily oral dosage of pioglitazone (10 mg/kg/day), linagliptin (10 mg/kg/day), and their combination were administered. Femur fractures were stabilized intramedullary. At weeks 2 and 6, rats were sacrificed for evaluation radiologically, biomechanically, histopathologically, histomorphometrically, and immunohistochemically. Results: Flexural strength of the L and PL groups were significantly higher compared to the P group. The highest healing score was in the L group and lowest in the P group, while the highest inflammation score was in the P group and lowest in the L group. A cluster of differentiation (CD) CD 34 reactivity was highest in the L group and lowest in the PL group. Conclusion: Linagliptin treatment significantly increased histological healing scores, callus volume, biomechanical strength, and vascularity, however, minimized the inflammatory process, which was increased by pioglitazone. The combination of linagliptin and pioglitazone restored BMD and increased biomechanical strength. Linagliptin monotherapy is rarely indicated; hence, T2DM patients with a high risk of bone fractures can be considered for combined therapy of pioglitazone and linagliptin.

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“…19 Another study combined both intratumoral and peritumoral expression of CD8 + T cells and FoxP3 + T cells into a single immune profile score and found lower score was an independent predictor of progress-free survival. 20 A large study analyzed 1476 RCC patients found PD-L1 expression was a strong predictor of increased CD8 T-cell infiltration and poor survival. 21 For metastatic ccRCCs, a study found PD-1 and PD-L1 were associated with worse disease features and PD-1 expression was associated with worse overall survival.…”

Section: Studies Related To Common Immune Biomarkersmentioning

confidence: 99%

Bridging radiomics to tumor immune microenvironment assessment in clear cell renal cell carcinoma

Shieh

Cen²,

Varghese³

et al. 2023

18th International Symposium on Medical Information Processing and Analysis

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Clear cell renal cell carcinoma (ccRCC) is a common cancer and could result in poor prognosis. Understanding individual tumor immune microenvironment (TIME) in ccRCC patients may predict prognosis and response to therapy. In this work, we explore the concept of using radiomic features extracted from computer tomography (CT) imaging to correlate the TIME measurements from multiplex immunohistochemistry (mIHC) analysis. Since CT imaging has long been the standard for evaluation of RCCs, it has the potential to provide noninvasive approximations of the tissue-based mIHC biomarkers. We selected two biomarkers that were grounded by clinical research: PD-L1 expression and CD8+PD-1+ T cell to CD8+ T cell ratio of the tumor epithelium. Then we extracted these two markers from a preliminary set of 52 patients using automated mIHC analysis. We used Random Forest, AdaBoost and ElasticNet to classify each sample as either expressing high or low levels of these markers. We found the radiomic features can correlate tumor epithelium PD-L1 >5%, PD-L1 >10%, and CD8+PD1+/CD8+>37% with AUROC 0.75, 0.85 and 0.71, respectively.

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Prognostic value of immunological profile based on CD8+ and FoxP3+ T lymphocytes in the peritumoral and intratumoral subsites for renal cell carcinoma

Cited by 8 publications

References 32 publications

Analysis of Immune Landscape Reveals Prognostic Significance of Cytotoxic CD4+ T Cells in the Central Region of pMMR CRC

Analysis of Immune Landscape Reveals Prognostic Significance of Cytotoxic CD4+ T Cells in the Central Region of pMMR CRC

Effects of Linagliptin and Pioglitazone on Fracture Healing in an Experimental Type 2 Diabetes Rat Model

Bridging radiomics to tumor immune microenvironment assessment in clear cell renal cell carcinoma

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