Dataset Information

Relationship between immune checkpoint proteins, tumour microenvironment characteristics, and prognosis in primary operable colorectal cancer.

ABSTRACT: The tumour microenvironment is an important factor for colorectal cancer prognosis, affecting the patient's immune response. Immune checkpoints, which regulate the immune functions of lymphocytes, may provide prognostic power. This study aimed to investigate the prognostic value of the immune checkpoints TIM-3, LAG-3 and PD-1 in patients with stage I-III colorectal cancer. Immunohistochemistry was employed to detect TIM-3, LAG-3, PD-1 and PD-L1 in 773 patients with stage I-III colorectal cancer. Immune checkpoint protein expression was assessed in tumour cells using the weighted histoscore, and in immune cells within the stroma using point counting. Scores were analysed for associations with survival and clinical factors. High tumoural LAG-3 (hazard ratio [HR] 1.45 95% confidence interval [CI] 1.00-2.09, p =?0.049) and PD-1 (HR 1.34 95% CI 1.00-1.78, p =?0.047) associated with poor survival, whereas high TIM-3 (HR 0.60 95% CI 0.42-0.84, p =?0.003), LAG-3 (HR 0.58 95% CI 0.40-0.87, p =?0.006) and PD-1 (HR 0.65 95% CI 0.49-0.86, p =?0.002) on immune cells within the stroma associated with improved survival, while PD-L1 in the tumour (p =?0.487) or the immune cells within the stroma (p =?0.298) was not associated with survival. Furthermore, immune cell LAG-3 was independently associated with survival (p =?0.017). Checkpoint expression scores on stromal immune cells were combined into a Combined Immune Checkpoint Stromal Score (CICSS), where CICSS 3 denoted all high, CICSS 2 denoted any two high, and CICSS 1 denoted other combinations. CICSS 3 was associated with improved patient survival (HR 0.57 95% CI 0.42-0.78, p =?0.001). The results suggest that individual and combined high expression of TIM-3, LAG-3, and PD-1 on stromal immune cells are associated with better colorectal cancer prognosis, suggesting there is added value to investigating multiple immune checkpoints simultaneously.

SUBMITTER: Al-Badran SS

PROVIDER: S-EPMC7869939 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Relationship between immune checkpoint proteins, tumour microenvironment characteristics, and prognosis in primary operable colorectal cancer.

Al-Badran Sara Sf SS Grant Lauren L Campo Maejoy V MV Inthagard Jitwadee J Pennel Kathryn K Quinn Jean J Konanahalli Prakash P Hayman Liam L Horgan Paul G PG McMillan Donald C DC Roxburgh Campbell Sd CS Roseweir Antonia A Park James H JH Edwards Joanne J

The journal of pathology. Clinical research 20201218 2

The tumour microenvironment is an important factor for colorectal cancer prognosis, affecting the patient's immune response. Immune checkpoints, which regulate the immune functions of lymphocytes, may provide prognostic power. This study aimed to investigate the prognostic value of the immune checkpoints TIM-3, LAG-3 and PD-1 in patients with stage I-III colorectal cancer. Immunohistochemistry was employed to detect TIM-3, LAG-3, PD-1 and PD-L1 in 773 patients with stage I-III colorectal cancer. ...[more]

PMID: 33338327

Similar Datasets

Project description:Background: The emergence of immune checkpoint inhibitors (ICIs) has opened a new chapter for the treatment of non-small cell lung cancer (NSCLC), and the best beneficiaries of ICI treatment are still being explored. Smoking status has been repeatedly confirmed to affect the efficacy of ICIs in NSCLC patients, but the specific mechanism is still unclear. Methods: We performed analysis on the Memorial Sloan Kettering Cancer Center (MSKCC) clinical NSCLC cohort receiving ICI treatment, The Cancer Genome Atlas (TCGA) Pan-Lung Cancer cohort, and Gene Expression Omnibus (GEO) database GSE41271 lung cancer cohort that did not receive ICI treatment, including survival prognosis, gene mutation, copy number variation, immunogenicity, and immune microenvironment, and explored the impact of smoking status on the prognosis of NSCLC patients treated with ICIs and possible mechanism. In addition, 8 fresh NSCLC surgical tissue samples were collected for mass cytometry (CyTOF) experiments to further characterize the immune characteristics and verify the mechanism. Result: Through the analysis of the clinical data of the NSCLC cohort treated with ICIs in MSKCC, it was found that the smokers in NSCLC receiving ICI treatment had a longer progression-free survival (HR: 0.69, 95% CI: 0.49–0.97, p = 0.031) than those who never smoked. Further analysis of the TCGA and GEO validation cohorts found that the differences in prognosis between different groups may be related to the smoking group’s higher immunogenicity, higher gene mutations, and stronger immune microenvironment. The results of the CyTOF experiment further found that the immune microenvironment of smoking group was characterized by higher expression of immune positive regulatory chemokine, and higher abundance of immune activated cells, including follicular helper CD4+ T cells, gamma delta CD4+ T cells, activated DC, and activated CD8+ T cells. In contrast, the immune microenvironment of non-smoking group was significantly enriched for immunosuppressive related cells, including regulatory T cells and M2 macrophages. Finally, we also found highly enriched CD45RAhighCD4+ T cells and CD45RAhighCD8+ T cells in the non-smoking group. Conclusion: Our research results suggest that among NSCLC patients receiving ICI treatment, the stronger immunogenicity and activated immune microenvironment of the smoking group make their prognosis better.

Project description:BACKGROUND: The percentage of tumour stroma (TSP) has recently been reported to be a novel independent predictor of outcome in patients with a variety of common solid organ tumours. The aim of this study was to examine the relationship between TSP, clinicopathological characteristics and outcome in patients with invasive ductal breast cancer, in particular node negative and triple negative disease. METHODS: A total of 361 patients with primary operable invasive ductal breast cancer were included in this study. The TSP was assessed visually on the haematoxylin and eosin-stained tissue sections. With a cutoff value of 50% TSP, patients with ≤ 50% stroma were classified as the low-TSP group and those with >50% stroma were classified as the high-TSP group. RESULTS: A total of 109 (30%) patients had high TSP. Patients with high TSP were old age (P=0.035), had more Her-2-positive tumours (P=0.029), low-grade tumour inflammatory infiltrate (P=0.034), low CD68+macrophage infiltrate (P<0.001), low CD4+ (P=0.023) and low CD8+ T-lymphocytes infiltrate (P=0.017), tumour recurrence (P=0.015) and shorter cancer-specific survival (P<0.001). In node-negative patients (n=207), high TSP was associated with low CD68+macrophage infiltrate (P=0.001), low CD4+ (P=0.040) and low CD8+ T-lymphocytes infiltrate (P=0.016) and shorter cancer-specific survival (P=0.005). In triple negative patients (n=151), high TSP was associated with high tumour grade (P=<0.001), lymph node positivity (P=0.027), low CD68+macrophage infiltrate (P=0.011) and shorter cancer-specific survival (P=0.035). The 15-year cancer-specific survival rate was 79% vs 21% in the low-TSP group vs high-TSP group. In multivariate survival analysis, a high TSP was associated with reduced cancer-specific survival in the whole cohort (P=0.001), node-negative patients (P=0.007) and those who received systemic adjuvant therapy (P=0.021), independent of other pathological characteristics including host inflammatory response. However, TSP was not an independent prognostic factor for triple negative patients (P=0.151). CONCLUSIONS: A high TSP in primary operable invasive ductal breast cancer was associated with recurrence and poorer long-term survival. The inverse relation with the tumour inflammatory infiltrate highlights the importance of the amount of tumour stroma on immunological response in patients with primary operable ductal breast cancer. Implementing this simple and reproducible parameter in routine pathological examination may help optimise risk stratification in patients with invasive ductal breast cancer.

Dataset Information

Relationship between immune checkpoint proteins, tumour microenvironment characteristics, and prognosis in primary operable colorectal cancer.

Publications

Relationship between immune checkpoint proteins, tumour microenvironment characteristics, and prognosis in primary operable colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure