The prognostic value of tumour-infiltrating lymphocytes (TILs) in pancreatic cancer: A systematic review and meta-analysis

Orhan, Adile; Vogelsang, Rasmus Peuliche; Andersen, Michael Brun; Madsen, Michael Tvilling; Hølmich, Emma Rosenkrantz; Raskov, Hans; Gögenür, Ismail

doi:10.1093/annonc/mdz447.006

“…Moreover, it has been reported that tumor secretion of TNF-α and IL-10 leads to lymphopenia and lymphocyte dysfunction [ 14 , 15 ]. As lymphocyte infiltration correlates with long-term oncological outcomes in pancreatic cancer, lymphopenia presents a means of immune evasion [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

“…Inflammation represents one of the key factors of tumor carcinogenesis. Based on histological analyses, a correlation of the magnitude of immune cell infiltration to the clinical outcome has been observed for patients with pancreatic cancer [ 2 ]. Moreover, there has been growing evidence for the predictive value of inflammatory biomarkers in regard to overall survival (OS) of cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Inflammation-Based Prognostic Scores in Pancreatic Cancer Patients—A Single-Center Analysis of 1294 Patients within the Last Decade

Neumann

¹

,

Schneider

²

,

Hilfenhaus

³

et al. 2023

Cancers

View full text Add to dashboard Cite

Inflammatory properties are known to promote tumor progression leading to an impaired median overall survival (mOS). Various small studies have focused on a wide range of inflammation-based prognostic indicators. By using sufficient data from 1294 out of 2323 patients diagnosed with pancreatic cancer between 2009 and 2021 at our cancer center, inflammatory markers such as the neutrophil to lymphocyte ratio (NRL), the platelet to lymphocyte ratio (PLR), the lymphocyte to monocyte ratio (LMR) and the CRP to albumin ratio (CAR) were evaluated. We identified a new combined score, termed the inflammatory benchmark index (IBI). We performed univariate and multivariate overall survival analyses and identified optimal prognostic cut-off values for each parameter. In univariate analyses, advanced age (p < 0.001), gender (p < 0.001), tumor stage (p < 0.001), CA19-9 (p = 0.001), NLR (p = 0.001), LMR (p = 0.004), PLR (p = 0.004), CAR (p = 0.001) and IBI (p = 0.001) were identified as prognostic markers. In multivariate analyses advanced age (p < 0.001), gender (p = 0.001), tumor stage (p < 0.001), CA19-9 (p < 0.001), NLR (p = 0.001), LMR (p = 0.038), CAR (p < 0.001) and IBI (p < 0.001) were independent prognostic markers. These findings emphasize the impact of inflammation in pancreatic cancer, provide easily accessible prognostic values for the clinician, and may be useful as stratification parameters for trials aimed at patient inflammation or immune response.

show abstract

“…Tumor-in ltrating lymphocytes can be readily assessed and are generally associated with more favorable clinicopathologic features and more favorable responses to chemotherapeutic regimens in a variety of neoplasms (32)(33)(34), including breast cancer (13,35,36). In a meta-analysis of more than 4000 breast cancer cases, 11% of samples were lymphocyte-predominant (i.e., having at least 50-60% lymphocyte in ltration), and 16% had zero TIL scores.…”

Section: Discussionmentioning

confidence: 99%

Characterization of immune checkpoints expression and lymphocyte densities of Iranian breast cancer patients; the co-expression status and clinicopathological associates

Pournabee

¹

,

Keshavarz-Fathi

²

,

Esmaeili

³

et al. 2023

Preprint

0

View full text Add to dashboard Cite

Background Breast malignancies are now the most common and deadliest type of neoplasms among women worldwide. Novel therapeutic approaches are needed to combat advanced stages of breast cancer. In this study, we aimed to investigate the expression and co-expression status of three immune checkpoints (PD-1, PD-L1, and LAG-3), as well as tumor-infiltrating lymphocytes (TIL) scores, and to further establish their potential correlations with clinicopathologic features. Methods We performed a retrospective study on 361 pathologic samples of breast cancer. Immunohistochemistry was performed to assess the status of the immune checkpoint markers, and H&E staining was used to score TILs. The correlations of the immune checkpoint markers of tumor cells and tumor-associated immune cells and TIL scores with clinicopathological characteristics were analyzed. Results Out of 361 assessed samples, LAG-3 was positive in 51%, while IC PD-L1 and TC PD-L1 were detectable in 36% and 8.9%, respectively. Moreover, both IC PD-L1 and LAG-3 stained positively in 24.4% of samples. IC PD-L1 expression was significantly higher in tumors with higher nuclear, mitotic, and overall grades and tubule formation. In addition, TC PD-L1 and LAG-3 exhibited a similar trend for higher overall grading. Tumors with positive estrogen- and progesterone-receptor (ER and PR) expression had significantly lower IC PD-L1 and TC PD-L1 staining, while LAG-3 positivity was more prevalent in HER2 positive samples. Tumors that were positive for these biomarkers had significantly higher Ki-67 scores. LAG-3 expression showed significant correlations with PD-1 and IC PD-L1 expression. Besides, the co-expression of LAG-3 and IC PD-L1 was significantly more encountered in luminal B and triple-negative subtypes, compared to the luminal A subtype. Regarding TILs, their scoring was significantly higher in ER and PR negative and HER2 positive samples. Intriguingly, samples with positive staining for LAG-3, IC PD-L1, and TC PD-L1 had significantly higher TIL scorings. Conclusions Immune checkpoints show differentially different levels of expression in certain molecular subtypes of breast cancer. Moreover, they reveal a meaningful correlation with each other, proliferation indices, and histologic grades. Finally, a sizable proportion of breast cancers co-express PD-L1 and LAG-3, which will make them appropriate targets for future combined ICIs.

show abstract

“…Tumor-infiltrating lymphocytes can be readily assessed and are generally associated with more favorable clinicopathologic features and more favorable responses to chemotherapeutic regimens in a variety of neoplasms [ 32 – 34 ], including breast cancer [ 13 , 35 , 36 ]. In a meta-analysis of more than 4000 breast cancer cases, 11% of samples were lymphocyte-predominant (i.e., having at least 50–60% lymphocyte infiltration), and 16% had zero TIL scores.…”

Section: Discussionmentioning

confidence: 99%

Characterization of immune checkpoints expression and lymphocyte densities of iranian breast cancer patients; the co-expression status and clinicopathological associates

Pournabee

¹

,

Keshavarz-Fathi

²

,

Esmaeili

³

et al. 2023

BMC Cancer

0

View full text Add to dashboard Cite

Background Breast malignancies are now the most common and deadliest type of neoplasms among women worldwide. Novel therapeutic approaches are needed to combat advanced stages of breast cancer. In this study, we aimed to investigate the expression and co-expression status of three immune checkpoints (PD-1, PD-L1, and LAG-3), as well as tumor-infiltrating lymphocytes (TIL) scores, and to further establish their potential correlations with clinicopathologic features. Methods We performed a retrospective study on 361 pathologic samples of breast cancer. Immunohistochemistry was performed to assess the status of the immune checkpoint markers, and H&E staining was used to score TILs. The correlations of the immune checkpoint markers of tumor cells and tumor-associated immune cells and TIL scores with clinicopathological characteristics were analyzed. Results Out of 361 assessed samples, LAG-3 was positive in 51%, while IC PD-L1 and TC PD-L1 were detectable in 36% and 8.9%, respectively. Moreover, both IC PD-L1 and LAG-3 stained positively in 24.4% of samples. IC PD-L1 expression was significantly higher in tumors with higher nuclear, mitotic, and overall grades and tubule formation. In addition, TC PD-L1 and LAG-3 exhibited a similar trend for higher overall grading. Tumors with positive estrogen- and progesterone-receptor (ER and PR) expression had significantly lower IC PD-L1 and TC PD-L1 staining, while LAG-3 positivity was more prevalent in HER2 positive samples. Tumors that were positive for these biomarkers had significantly higher Ki-67 scores. LAG-3 expression showed significant correlations with PD-1 and IC PD-L1 expression. Besides, the co-expression of LAG-3 and IC PD-L1 was significantly more encountered in luminal B and triple-negative subtypes, compared to the luminal A subtype. Regarding TILs, their scoring was significantly higher in ER and PR negative and HER2 positive samples. Intriguingly, samples with positive staining for LAG-3, IC PD-L1, and TC PD-L1 had significantly higher TIL scorings. Conclusions Immune checkpoints show differentially different levels of expression in certain molecular subtypes of breast cancer. Moreover, they reveal a meaningful correlation with each other, proliferation indices, and histologic grades. Finally, a sizable proportion of breast cancers co-express PD-L1 and LAG-3, which will make them appropriate targets for future combined ICIs.

show abstract

The prognostic value of tumour-infiltrating lymphocytes (TILs) in pancreatic cancer: A systematic review and meta-analysis

Cited by 4 publications

References 0 publications

Inflammation-Based Prognostic Scores in Pancreatic Cancer Patients—A Single-Center Analysis of 1294 Patients within the Last Decade

Inflammation-Based Prognostic Scores in Pancreatic Cancer Patients—A Single-Center Analysis of 1294 Patients within the Last Decade

Characterization of immune checkpoints expression and lymphocyte densities of Iranian breast cancer patients; the co-expression status and clinicopathological associates

Characterization of immune checkpoints expression and lymphocyte densities of iranian breast cancer patients; the co-expression status and clinicopathological associates

Contact Info

Product

Resources

About