Increased CD3+, CD8+, or FoxP3+ T Lymphocyte Infiltrations Are Associated with the Pathogenesis of Colorectal Cancer but Not with the Overall Survival of Patients

Barbosa, Amanda Pires; Martinho, Olga; Nogueira, Rosete; Campos, Jorge; Lobo, Liliana; Pinto, Henrique Motta; Longatto‐Filho, Adhemar; Martins, Sandra F.; Torrado, Egídio

doi:10.3390/biology10080808

Cited by 9 publications

(8 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This phenomenon is not consistent with the majority of other results [26,27]. However, a number of studies also failed to show the expected correlation-entirely or, at least, in some of the analyzed cohorts [28][29][30][31]. It is speculated that the lack of correlation between density of TILs and survival or other prognostic factors (e.g., stage of disease) may be due to environmental variables, such as the microbiome or tumor inflammatory status [32,33].…”

Section: Discussionmentioning

confidence: 65%

Correlation between Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR) and Tumor-Infiltrating Lymphocytes (TILs) in Left-Sided Colorectal Cancer Patients

Gawiński

Michalski

Mróz

et al. 2022

Biology

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Novel markers are required in order to select high-risk patients and better adjust the treatment. Both peripheral and local markers of cancer-related inflammation (CRI) such as lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) and tumor-infiltrating lymphocytes (TILs) have been thoroughly investigated in recent years and deemed to be highly prognostic. We hypothesized that there is an association between local and peripheral CRI indices and that blood-based biomarkers may serve as a surrogate of TILs. We retrospectively analyzed 87 patients with locally advanced left-sided CRC treated with radical-intent surgery in the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland, between January 2014 and December 2015. Fifty patients were found eligible for the study. The patients were divided in terms of pre-treatment values of systemic inflammatory response (SIR) markers into LMR/NLR/PLR-high and low groups. We evaluated the resected specimens by immunohistochemistry in order to assess the densities of CD3+ and CD8+ lymphocytes in the center of the tumor and in the invasive margin. We found that the level of CD3+ lymphocytes in the center of the tumor was statistically significantly higher in patients with low pre-treatment NLR (p = 0.044); however, no correlation between any of the SIR markers and CD3+ or CD8+ TILs was observed. Five-year overall survival (OS) was longer in patients with high LMR (p < 0.001), low NLR (p = 0.001) and low PLR (p = 0.095). No correlation between the density of TILs and OS was demonstrated. In conclusion, based on our study, peripheral blood-based markers and CD3+ and CD8+ TILs are not interrelated.

show abstract

Section: Discussionmentioning

confidence: 65%

Correlation between Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR) and Tumor-Infiltrating Lymphocytes (TILs) in Left-Sided Colorectal Cancer Patients

Gawiński

Michalski

Mróz

et al. 2022

Biology

View full text Add to dashboard Cite

show abstract

“…Accordingly, in the present study, we assessed the CD3 and CD8 expressions in the IM and CT to evaluate their prognostic potential in CRC, however similar to Barbosa et al. ( 42 ), no statistically significant association was found in the total cohort. Since proximal and distal CRC displays distinct epidemiological, pathological, and clinical entities ( 2 , 3 ), we further analyzed TILs infiltration and their association with clinical outcomes based on the tumor location.…”

Section: Discussionmentioning

confidence: 65%

Tim3 and PD-1 as a therapeutic and prognostic targets in colorectal cancer: Relationship with sidedness, clinicopathological parameters, and survival

et al. 2023

View full text Add to dashboard Cite

BackgroundColorectal cancer (CRC) is a heterogeneous disease that complicates predicting patients’ prognosis and their response to treatment. CRC prognosis is influenced by the tumor microenvironment (TME). The immune system is a critical component of the TME. Programmed cell death receptor 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (Tim3) are inhibitory immune checkpoints that regulate immune response and may provide prognostic power. However, the effect of their expressions and co-expressions on the CRC prognosis remains unclear. Accordingly, this study aimed to investigate the prognostic value of the CD8, CD3, PD-1, Tim3 expression, and PD-1/Tim3 co-expression in patients with CRC.Materials and MethodsOne hundred and thirty six patients with CRC who underwent curative surgery were enrolled in the study. Immunohistochemical staining was performed for PD-1, Tim3, CD8, and CD3, and the expression of each marker was evaluated in the center of the tumor (CT), invasive margin (IM), and adjacent normal-like tissue.ResultOur results indicated that high expression of PD-1 in IM was significantly associated with lower TNM stage, T-stage, M-stage, lack of metastasis, the presence of tertiary lymphoid structure (TLS), lack of recurrence (in the left-sided tumors), and larger tumor size (in right-sided tumors) (P<0.05). High expression of PD-1 in IM was also associated with improved overall survival (OS) in a subgroup of patients with high CD8 expression. High Tim3 expression in CT was associated with higher M-stage (M1) (in left-sided CRCs) (P<0.05). It was also associated with decreased OS in total cohort and left-sided CRCs and represented an independent prognostic factor for CRC patients in multivariate analysis. PD-1 and Tim3 co-expression had no synergistic effects on predicting OS.ConclusionOur findings suggest that the clinicopathological and prognostic significance of immune system-related markers such as CD8, PD-1, and Tim3 depends on the primary tumor sides. We also showed that Tim3 could act as a prognostic factor and therapeutic target in CRC. This marker is probably a more preferred target for immunotherapy than PD-1, especially in left-sided CRCs.

show abstract

“…Similar observations were made by other authors who showed that high densities of tumor-infiltrating CD8 + cells are associated with improved disease-free and overall survival in CRC, and the high immune cell infiltration by cytotoxic CD8 + T-cells has a favorable prognostic significance 35 . Additionally, it was shown that the presence of high infiltrations of CD3 +, CD8 + lymphocytes in the tumor margins was associated with TNM stages I-II and the absence of lymph node metastases 36 .…”

Section: Discussionmentioning

confidence: 99%

Simultaneous analysis of tumor-infiltrating immune cells density, tumor budding status, and presence of lymphoid follicles in CRC tissue

Markowski¹,

Markowska

Ustymowicz

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Colorectal cancer (CRC) affects more than 1,000,000 people worldwide each year. Recently, the number of young patients with early-onset colorectal cancer has increased, and right-sided colorectal cancer is still often diagnosed only in advanced stages. The TNM classification is not perfect for CRC staging. This study aimed to perform, for the first time, simultaneous analysis of tumor-infiltrating immune cell density, presence of lymphoid follicles, and budding status in CRC tissue. Intraoperative samples of neoplastic tissue were collected from 195 consecutive patients who were admitted to the surgical ward for elective colorectal surgery. Histological parameters were assessed in the tissue samples: tumor budding foci, poorly differentiated clusters and areas of poorly differentiated components. Tumor-infiltrating immune cells (tumor-associated neutrophils and tumor-infiltrating lymphocytes) were detected in five randomly chosen, areas at the tumor center and at the invasive front. Additionally, the presence of lymphoid follicles in CRC tissue was assessed. Tumor budding parameters were positively correlated with colorectal cancer advancement or histologic (mucinous) type of CRC. The number of poorly differentiated clusters was higher in younger patients. Lower densities of CD3 and CD4 lymphocytes were seen in CRC with a greater depth of tumor invasion. Lower densities of CD3 and CD8 lymphocytes were found in CRC with metastases to the surrounding lymph nodes. The lower density of CD8 lymphocytes was observed in CRC with distant metastases. Lower densities of tumor-associated neutrophils and tumor-infiltrating lymphocytes (CD3 and CD8) were revealed in CRC without lymphoid follicles. The number of lymphoid follicles was higher in patients with less advanced CRCs. Three histopathology markers, such as high tumor budding, scanty lymphocyte infiltration, and the poverty of lymphoid follicles, complement each other, appear to be reliable indicators of colorectal cancer progression, and could be useful in everyday medical practice, but their widespread use requires further research. We propose to take into account these markers, in the assessment of colorectal cancer advancement, in addition to the TNM classification.

show abstract

Increased CD3+, CD8+, or FoxP3+ T Lymphocyte Infiltrations Are Associated with the Pathogenesis of Colorectal Cancer but Not with the Overall Survival of Patients

Cited by 9 publications

References 55 publications

Correlation between Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR) and Tumor-Infiltrating Lymphocytes (TILs) in Left-Sided Colorectal Cancer Patients

Correlation between Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR) and Tumor-Infiltrating Lymphocytes (TILs) in Left-Sided Colorectal Cancer Patients

Tim3 and PD-1 as a therapeutic and prognostic targets in colorectal cancer: Relationship with sidedness, clinicopathological parameters, and survival

Simultaneous analysis of tumor-infiltrating immune cells density, tumor budding status, and presence of lymphoid follicles in CRC tissue

Contact Info

Product

Resources

About