Clinicopathological significance and prognostic role of tumor-infiltrating lymphocytes in colorectal cancer

Purpose: This study aimed to elucidate the clinicopathological significance and prognostic role of tumor-infiltrating lymphocytes in colorectal cancer. Methods: The immunohistochemistry of CD3 and CD8 was performed on 265 human colorectal cancer tissues to investigate the tumor-infiltrating lymphocytes using Immunoscore. The correlation between Immunoscore and clinicopathological characteristics, including survival rates, was elucidated. In addition, the impact of tumor-infiltrating lymphocytes on programmed death-ligand 1 (PD-L1) protein expression was evaluated through immunohistochemistry. Results: Of the 265 colorectal cancer tissues, 40.8% had high Immunoscore, while 59.2% had low Immunoscore. A high Immunoscore was significantly correlated with favorable tumor behaviors, including lower rates of vascular, lymphatic, and perineural invasion; lymph node metastasis; and distant metastasis. PD-L1 expressions of tumor and immune cells were significantly higher in patients with high Immunoscore than in those with low Immunoscore. In addition, colorectal cancer tissues with high CD8-positive lymphocytes showed higher PD-L1 expressions of tumor and immune cells than colorectal cancer tissues with low CD8-positive lymphocytes. There was a significant correlation between high Immunoscore and better overall survival. However, there was no significant difference in survival rate according to PD-L1 expressions of tumor and immune cells in high and low Immunoscore subgroups. Conclusions: Taken together, our results showed that high tumor-infiltrating lymphocytes were significantly correlated with favorable tumor behaviors and better survival. In addition, there was a significant correlation between PD-L1 expression and tumor-infiltrating lymphocytes.

Download Full-text

Clinicopathological significance and prognostic implication of programmed death-1 ligand 2 expression in colorectal cancer

The International Journal of Biological Markers ◽

10.1177/1724600819858753 ◽

2019 ◽

Vol 34 (3) ◽

pp. 276-283 ◽

Cited By ~ 1

Author(s):

Jung-Soo Pyo ◽

Byoung Kwan Son ◽

Kwang Hyun Chung ◽

Il Hwan Oh

Keyword(s):

Colorectal Cancer ◽

Immune Cells ◽

Survival Rates ◽

Node Metastasis ◽

Programmed Death ◽

Tumor Node Metastasis Stage ◽

Significant Difference ◽

Clinicopathological Significance ◽

Programmed Death 1 ◽

The Impact

Purpose: The aim of this study was to evaluate the clinicopathological significance and prognostic role of programmed death-1 ligand 2 (PD-L2) expression in colorectal cancer according to intratumoral components. Methods: We used immunohistochemical analysis to investigate the impact of PD-L2 expression on clinicopathological characteristics and survival in 264 human colorectal cancer tissues. We also evaluated the correlation between PD-L2 expression and PD-L1 expression. Results: PD-L2 was expressed in 17.4% of the tumors (T-PD-L2) and in 19.3% of the immune cells (I-PD-L2) of the 264 CRC tissues. I-PD-L2 expression was significantly correlated with favorable tumor behaviors, including lower pathologic tumor stage, less lymph node metastasis, less distant metastasis, and lower pathologic tumor node metastasis stage. There was no significant correlation between I-PD-L2 expression and T-PD-L2 expression ( P = 0.091). However, I-PD-L2 expression was correlated with PD-L1 expression in the immune cells ( P < 0.001). There was also a significant correlation between high Immunoscore and I-PD-L2, but not T-PD-L2 ( P < 0.001 and P = 0.190, respectively). The prognosis was better for patients who expressed I-PD-L2 than for patients who did not. In patients who expressed I-PD-L2, there was a significant difference in the survival rate between subgroups according to the presence or absence of T-PD-L2 expression. Conclusions: Our results suggest that I-PD-L2 expression is significantly correlated with favorable tumor behaviors and better survival rates. There is also a significant correlation between PD-L2 expression and PD-L1 expression in immune cells.

Download Full-text

Prognostic role of CD8+ tumor-infiltrating lymphocytes in stage III colorectal cancer with and without microsatellite instability

Human Pathology ◽

10.1016/j.humpath.2004.01.022 ◽

2004 ◽

Vol 35 (7) ◽

pp. 808-816 ◽

Cited By ~ 146

Author(s):

F PRALL

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Tumor Infiltrating Lymphocytes ◽

Stage Iii ◽

Prognostic Role ◽

Infiltrating Lymphocytes

Download Full-text

Prognostic role of CD8+ tumor infiltrating lymphocytes in stage III colorectal cancer with and without microsatellite instability

Pathology - Research and Practice ◽

10.1016/s0344-0338(04)80716-7 ◽

2004 ◽

Vol 200 (4) ◽

pp. 340

Author(s):

F. Prall ◽

T. Dührkop ◽

V. Weirich ◽

C. Ostwald ◽

H. Nizze ◽

...

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Tumor Infiltrating Lymphocytes ◽

Stage Iii ◽

Prognostic Role ◽

Infiltrating Lymphocytes

Download Full-text

Prognostic Role of Tumor‐Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma

The Laryngoscope ◽

10.1002/lary.29589 ◽

2021 ◽

Author(s):

Yukiko Hori ◽

Akira Kubota ◽

Tomoyuki Yokose ◽

Madoka Furukawa ◽

Takeshi Matsushita ◽

...

Keyword(s):

Tumor Infiltrating Lymphocytes ◽

Tumor Budding ◽

Tongue Carcinoma ◽

Oral Tongue ◽

Prognostic Role ◽

Infiltrating Lymphocytes

Download Full-text

Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes

The Oncologist ◽

10.1634/theoncologist.2019-0611 ◽

2020 ◽

Vol 25 (6) ◽

pp. 481-487 ◽

Cited By ~ 13

Author(s):

Fotios Loupakis ◽

Ilaria Depetris ◽

Paola Biason ◽

Rossana Intini ◽

Alessandra Anna Prete ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Mismatch Repair ◽

Checkpoint Inhibitors ◽

Tumor Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes

Download Full-text

Role of the Pathologist in the Diagnosis of Hereditary Non-Polyposis Colorectal Cancer

Disease Markers ◽

10.1155/2004/197484 ◽

2004 ◽

Vol 20 (4-5) ◽

pp. 215-224 ◽

Cited By ~ 26

Author(s):

Jeremy R. Jass

Keyword(s):

Colorectal Cancer ◽

Mismatch Repair ◽

Tumor Infiltrating Lymphocytes ◽

Dna Mismatch ◽

Repair Deficiency ◽

Dna Mismatch Repair Genes ◽

Histological Criteria ◽

Dna Microsatellite ◽

Infiltrating Lymphocytes

The aim of this paper is to indicate how the pathologist may suspect a diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) on the basis of histological criteria and patient age alone. A single morphological feature, namely the presence of intra-epithelial lymphocytes (tumor infiltrating lymphocytes), identifies the majority of colorectal cancers (CRC) with the DNA microsatellite instability-high phenotype. A number of pathological criteria can help to distinguish HNPCC from sporadic MSI-H CRC, though age below 60 years is an important pointer towards HNPCC. Immunohistochemistry to demonstrate loss of expression of DNA mismatch repair genes serves as a highly reliable test of mismatch repair deficiency if antibodies to hMLH1, hMSH2, hMSH6 and hPMS2 are employed.

Download Full-text

Development and Validation of a Prognostic Autophagy-Related Gene Pair Index Related to Tumor-Infiltrating Lymphocytes in Early-Stage Lung Adenocarcinoma

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.719011 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zi-Hao Wang ◽

Yu Li ◽

Pei Zhang ◽

Xuan Xiang ◽

Xiao-Shan Wei ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Gene Pair ◽

Early Stage ◽

Tumor Infiltrating Lymphocytes ◽

Related Gene ◽

Tumor Immune Escape ◽

Cox Regression Analysis ◽

Significant Difference ◽

Infiltrating Lymphocytes

The role of autophagy in lung cancer is context-dependent and complex. Recent studies have reported the important role of autophagy in tumor immune escape. However, the association between autophagy and tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma (LUAD) remains unclear. In this study, we aimed to develop and validate the autophagy-related gene pair index (ATGPI) and autophagy clinical prognostic index (ACPI) in multiple LUAD cohorts, including The Cancer Genome Atlas (TCGA) cohort, Gene Expression Omnibus cohorts, and one cohort from Union Hospital, Wuhan (UH cohort), using a Cox proportional hazards regression model with the least absolute shrinkage and selection operator. Multivariate Cox regression analysis demonstrated that there was a significant difference in overall survival (OS) between patients with high and low ATGPI in the testing [hazard ratio (HR) = 1.97; P < 0.001] and TCGA validation (HR = 2.25; P < 0.001) cohorts. Time-dependent receiver operating characteristic curve analysis was also performed. We found that high ATGPI could accurately identify patients with early-stage LUAD with shorter OS, with the areas under the curve of 0.703 and 0.676 in the testing and TCGA validation cohorts, respectively. Concordance index (C-index) was used to evaluate the efficiency of ATGPI and ACPI. The C-index of ACPI was higher than that of ATGPI in the testing (0.71 vs. 0.66; P < 0.001), TCGA validation (0.69 vs. 0.65; P = 0.028), and UH (0.80 vs. 0.70; P = 0.015) cohorts. TIL analysis demonstrated that the proportions of tumor-infiltrating CD4+ T cells were lower in the high-ATGPI group than in the low-ATGPI group in both the TCGA validation and UH cohorts. These results indicate the potential clinical use of ATG signatures which are associated with TILs, in identifying patients with early-stage LUAD with different OS.

Download Full-text

Addition of immunotherapy in adjuvant setting could be a promising avenue of colorectal cancer (CRC) treatment, especially in patients with higher levels of programmed cell death ligand-1 (PD-L1) positive circulating epithelial tumor cells (CETC) after neoadjuvant chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14036 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14036-e14036

Author(s):

Monika Pizon ◽

Dorothea Schott ◽

Ulrich A. Pachmann ◽

Katharina Pachmann ◽

Siddarth Agrawal ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Tumor Cells ◽

Tumor Infiltrating Lymphocytes ◽

Histological Subtypes ◽

Epithelial Tumor ◽

Clinicopathologic Factors ◽

Infiltrating Lymphocytes ◽

The Impact ◽

Promising Avenue

e14036 Background: CRC is the third most frequent cancer in men and second in women worldwide. Recently, immune checkpoint molecules such as PD-1/PD-L1 have been identified as a possible target for immunotherapy in CRC and are increasingly being tested in clinical trials in combination with chemotherapy. However, the role of PD-L1 expression in CRC tumor cells and its interaction with other clinicopathologic factors remains elusive. In this study, we evaluated the impact of neoadjuvant chemotherapy on the fraction of PD-L1 positive CETCs and to compare its expression to the primary tumor. Methods: CETCs were determined from the blood of 20 patients suffering from CRC in different stages of the disease. The number of CETCs and their expression of PD-L1 were investigated using the maintrac method. In parallel, PD-L1 expression and tumor infiltrating lymphocytes (TILs) were assessed by immunohistochemistry on tissue biopsies. Results: PD-L1 expression could be assessed in all patients with detectable CETCs with a median of 50%. CETCs were more frequently found to be PD-L1 positive than tissue, and no correlation was observed between tissue and CETCs PD-L1 expression. Interestingly, patients with neoadjuvant chemotherapy had more positive PD-L1 CETCs compared to patients without chemotherapy (mean 66,7 vs. 35,2 p < 0.05), but the total number of CETCs was significantly lower in the neoadjuvant group. Also, patients with mucinous adenocarcinoma had more PD-L1 positive CETCs compared to other histological subtypes. The number of TILs was higher in patients with lymph node metastasis and larger tumors. TILs count did not differ in patients with and without neoadjuvant chemotherapy. Conclusions: Assessment of PD-L1 expression in CETCs is feasible, and CETCs are more often positive than in tissue. PD-L1 expression on CETCs was higher in patients who received neoadjuvant chemotherapy. Further studies are necessary to validate these findings.

Download Full-text