Prognostic role of tumour-infiltrating T lymphocytes in stage IIA (T3N0) colon cancer: A broad methodological study in a fairly homogeneous population

Zengin, Mehmet

doi:10.1016/j.anndiagpath.2019.05.007

Cited by 15 publications

(11 citation statements)

References 37 publications

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“…For example, in CRC patients, whether in tumour stroma or cancer cell nests, a strong T cell infiltration is consistently associated with cancer-specific prognosis, regardless of nodal state and stage. That is, a massive T-cell infiltration, indicative of a coordinated adaptive immune response, appears to be one of the most important factors in predicting the outcome for patients resected for CRC [38]. In this study, we found that LIR was significantly lower in tumours expressing CXCL12 and CXCR4.…”

Section: Discussionsupporting

confidence: 48%

Evaluation of CXCL12 and CXCR4 to predict poor survival in lymph node-positive colorectal cancer patients

Zengin¹,

Dursun²,

Behzatoğlu³

et al. 2020

pjp

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It is well known that interactions in the tumour microenvironment are very important in the progression of tumours. We investigated the relationship between chemokine ligand type 12 (CXCL12), chemokine receptor type 4 (CXCR4) and survival in advanced colorectal cancers (CRC). Primary tumour samples of stage III-IV CRC patients were investigated for CXCL12 and CXCR4. Chemokine ligand type 12 and CXCR4 expressions were significantly associated with poor prognostic factors (e.g. for CXCL12: lymphatic invasion [p = 0.009], positive surgical margin [p = 0.006], advanced stage [p = 0.028], etc.). Also, these parameters were independent risk factors for low LIR (e.g. for CXCL12: Odds ratio [OR] = 2.27, p = 0.001) and low tumour stroma-ratio (TSR; e.g. for CXCL12: OR = 1.18, p = 0.003). In univariate analysis, 5-year RFS and OS were poor (e.g. for CXCL12: RFS, p < 0.001 and OS, p = 0.001). Multivariate analysis showed that these parameters were independent poor survival parameters for RFS and OS (e.g. for CXCL12: Hazard ratio [HR] = 3.54 [CI: 1.52-4.67], p = 0.001 and HR = 2.74 [1.48-4.71], p = 0.025). We showed that CXCL12 and CXCR4 expressions are poor prognostic factors in lymph node-positive CRC patients and are associated with low TSR and low LIR.

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Section: Discussionsupporting

confidence: 48%

Evaluation of CXCL12 and CXCR4 to predict poor survival in lymph node-positive colorectal cancer patients

Zengin¹,

Dursun²,

Behzatoğlu³

et al. 2020

pjp

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“…Briefly, histopathological evaluations can be divided intrabiopsy evaluation (section, area and focus) and extrabiopsy evaluation (staining, magnification, and counting). Model A [17] was used for intrabiopsy evaluation and method 1 [18] was used for extrabiopsy evaluation. And both of these methods yielded successful results.…”

Section: Discussionmentioning

confidence: 99%

“…Many different methods have been used in the literature to evaluate BD [8][9][10][11][12][13][14]. This study was based on two successful methods, model A and method 1 [17,18]. Model A recommends using the hot spot area, deepest invasive block, invasive margin.…”

Section: Optimal Evaluation Methodsmentioning

confidence: 99%

“…Four 4-µm thick sections (n = 328) were cut from each block, two of them stained with hematoxylin and eosin (H & E), the rest stained with IHC. Pathological evaluation of the primary tumor was performed according to the American Joint Cancer Classification Committee [17]. All sections were evaluated separately by three experienced pathologists and the final value was given according to the average of these observers.…”

Section: Samplesmentioning

confidence: 99%

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Tumour budding in preoperative biopsy specimens is a useful prognostic index for identifying high-risk patients in early-stage (pN0) colon cancer

Zengin

Çi̇fci̇

2020

Turk J Med Sci

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Background/aim: Tumour budding (BD) is considered a valuable prognostic factor in colon cancer (CC), but its use in daily practice is uncertain. We investigated the prognostic effect of BD using preoperative biopsy specimens in a fairly homogeneous population. Materials and methods: Eighty-two (pN0) CC patients who underwent surgery after preoperative biopsy between 1997 and 2013 were included in the study. Model A (using the 'deeply invasive blocks & hot-spot area & invasive margin) and method 1 (using the '20× objective & immunohistochemistry staining & quantitive counting') were used as standard methods. Results: High BD was significantly associated with poor prognostic factors (lymphatic invasion [P = 0.008], perineural invasion [P = 0.041], advanced pT [P = 0.015], invasive margin [P = 0.008], and margin involvement [P = 0.019]). Moreover, correlations between different BD estimates (r = 0.613-0.696), reproducibility of study (Κappa = 0.68-0.73), and usefulness of cutoff value (area of under ROC = 0.746 [0.663-0.829]) were well. In univariate analysis, 5-year survival was poor in patients with high BD (relaps-free survival

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“…Large numbers of functional cytotoxic tumor-infiltrating lymphocytes (TILs) correlate with increased progression-free survival for GBM patients [17][18][19][20]. However, the immunosuppressive milieu of GBM impairs T cell cytolytic function, reducing the effectiveness of T cell based therapies for treating GBM [21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Neural Stem Cells Secreting Bispecific T Cell Engager to Induce Selective Anti-Glioma Activity

Pituch

Zanikou

Ilut

et al. 2020

Preprint

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Glioblastoma (GBM) is the most lethal primary brain tumor in adults. There is no treatment that provides durable relief for the vast majority of GBM patients. In this study, we’ve tested a bispecific antibody comprised of single-chain variable regions (scFvs) against T cell CD3ε and GBM cell interleukin 13 receptor alpha 2 (IL13Rα2). We demonstrate that this BiTE (BiTELLON) engages peripheral and tumor-infiltrating lymphocytes harvested from patient’s tumors, and in so doing exerts anti-GBM activity ex vivo. The interaction of BiTELLON with T cells and engagement of IL13Rα2-expressing GBM cells stimulates T cell proliferation as well as production of pro-inflammatory cytokines INFγ and TNFα. We have modified neural stem cells (NSCs) to produce and secrete the BiTE (NSCsLLON). When injected intracranially in mice with brain tumor, NSCsLLON show tropism for tumor, secrete BiTELLON, and remain viable for several days. When injected directly into tumor, NSCLLON provide significant survival benefit to mice bearing IL13Rα2+ GBM. Our results support further investigation and development of this therapeutic for clinical translation.

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Prognostic role of tumour-infiltrating T lymphocytes in stage IIA (T3N0) colon cancer: A broad methodological study in a fairly homogeneous population

Cited by 15 publications

References 37 publications

Evaluation of CXCL12 and CXCR4 to predict poor survival in lymph node-positive colorectal cancer patients

Evaluation of CXCL12 and CXCR4 to predict poor survival in lymph node-positive colorectal cancer patients

Tumour budding in preoperative biopsy specimens is a useful prognostic index for identifying high-risk patients in early-stage (pN0) colon cancer

Neural Stem Cells Secreting Bispecific T Cell Engager to Induce Selective Anti-Glioma Activity

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