Prognostic impact of tumour‐infiltrating B cells and plasma cells in colorectal cancer

Abstract

Multiple studies have described associations between infiltrating immune cells and prognosis in cancer; however, the clinical relevance has most often been attributed to the T-cell linage. This study aimed to further investigate the clinicopathological correlates and prognostic impact of B cell and plasma cell infiltration in CRC. Immunohistochemical expression of CD20, CD138 and immunoglobulin kappa C (IGKC) was analysed in tissue microarrays with tumours from 557 incident cases of CRC from a prospective population-based cohort. Kaplan-Meier analysis and Cox regression analysis were used to determine the impact of CD20, CD138 and IGKC expression on 5-year overall survival. Immune cell-specific CD20, CD138, and IGKC expression correlated significantly with lower T-stage (p < 0.001, p < 0.001, and p = 0.006, respectively). A higher density of CD20+ cells correlated significantly with an improved OS (HR = 0.53, 95% CI 0.36-0.78), remaining significant in multivariable analysis adjusted for age, TNM stage, differentiation grade and vascular invasion (HR = 0.51; 95% CI 0.33-0.80). Immune cell-specific CD138 and IGKC expression correlated significantly with an improved OS in univariable Cox regression analysis; however, these associations did not remain significant in multivariable analysis. Finally, tumour cell-specific CD138 expression was found to be an independent factor of poor prognosis (HR 1.52; 95% CI 1.03-2.24). The results from the present study demonstrate that B cell infiltration in CRC has a significant impact on tumour progression and prognosis. These findings supplement and extend the current knowledge of the immune landscape in colorectal cancer, and merit further study.

High Density of Tumor-infiltrating B-Lymphocytes and Plasma Cells Signifies Prolonged Overall Survival in Adenocarcinoma of the Esophagogastric Junction

“…High B-cell density is said to be associated with improved outcome in gastric, breast and colorectal cancer (9)(10)(11), as well as squamous cell carcinoma of the tongue (12), melanoma and hepatocellular carcinoma (5,13). The same correlation has been shown for pancreatic adenocarcinomas, though here the impact was only measurable if cells were arranged in the pattern of TLSs (4,14).…”

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

“…Since the prognostic value of B lymphocytes, plasma cells and various subsets of T lymphocytes has previously been shown do differ according to PTL in the herein investigated cohort, 14 , 15 their associations with PD-1 and PD-L1 expression were also examined. There were significant correlations between PD-1 expression and T and B cell infiltration, being most evident in right-sided tumours (Table 1).…”

“…14 , 15 , 54 , 55 The Malmö Diet and Cancer Study is a prospective population-based cohort with the primary aim to investigate associations between various dietary factors and cancer incidence. 56 The project, including non- participants in the European Prospective Investigation into Cancer (EPIC) cohort, enrolled 18326 women (60.2%) and 12120 (39.8%) men, with a total of 30446 participants (from a background population of 74,138).…”

“…The density of B cells (CD20 + ), plasma cells (CD138 + , IGKC + ) and T lymphocytes (CD3 + , CD8 + , FoxP3 + ) was analysed as previously described. 14 , 15 …”

The functional role of B cells and their secreted antibodies

“…To date, there is a controversy, since several studies suggest that TIBs are protective [164][165][166] , while others indicate that Bregs are increased in patients with solid tumours, which is associated with increased aggressiveness and inferior patients' outcome [167][168][169][170][171] . In lymphoid malignancies, the anti-tumour immune responses are suppressed by malignant B cells that 'perform' as Bregs via the expression of suppressive ligands [172][173][174] .…”