Introduction
Although the prognostic significance of cellular components of the immune system has been investigated in several solid neoplasms and is well established, the role of plasma cells in the tumor microenvironment has been neglected and only recently these cells are increasingly being appreciated as key players in the tumor microenvironment.
Aims & Methods
The purpose of our study is to explore the contribution of plasma cells to the immune microenvironment of colorectal adenocarcinomas and describe their correlation with prognosis.
In our study, a total of 108 patients with colorectal adenocarcinoma were included [68 men/40 women, median age (IQR): 70 (64-76) years, I-IV stage (AJCC/TNM 8th edition)] who underwent surgical resection between January 2004 to May 2008. Histological slides and paraffin blocks were retrieved from the archives of the Department of Pathology, Attikon University Hospital. Tissue microarrays (TMAs) of 2 mm diameter were constructed with representative areas from the center and periphery of the tumor. Immunohistochemical stains were performed on TMAs to detect the presence of plasma cells (CD138) and cells of adaptive immunity (CD3, CD4, CD8, CD20). Tertiary lymphoid structures (TLS) were assessed on hematoxylin-eosin-stained slides. Depending on the number of plasma cells, the cases were classified into the following categories: absence of plasma cells or presence of rare single cells, presence of rare small aggregates (>5 cells/aggregation), presence of frequent aggregates, presence of large aggregates or sheets of plasma cells. Clinical and pathologic information was acquired from hospital medical records including patient’s outcome and survival.
Results
Ιncreased number of plasma cells (presence of frequent aggregates, presence of large aggregates or sheets of plasma cells) was observed in 70 cases (65%), while absence or rare aggregates of plasma cells was demonstrated 38 cases (35 %). The presence of large aggregates or sheets of plasma cells in the tumor was significantly associated with the presence of TLS (p=0.004) and tumor infiltration by increased numbers of CD3+, CD8+ T, and CD20+ B lymphocytes compared with the absence of plasma cells or the presence of rare single plasma cells (p=0.025, p=0.012, p=0.001, respectively). Moreover, it was reported that the presence of an increased number of plasma cells compared with the absence of plasma cells in the center of the tumor is significantly correlated to a more favorable prognosis (77 vs 47 months; p=0.047; p<0.05).
Conclusion
In patients with colorectal adenocarcinoma, the presence of high densities of plasma cells in the tumor bed may be associated with increased adaptive immune cell populations in the tumor environment, as well as with longer patient’s survival. Consequently, a careful evaluation of plasma cells and a better understanding of their role in the tumor microenvironment of colorectal cancer seems to be crucial in order to design efficient immunotherapeutic strategies.
References
1.Galon et al. Tumor immunology and tumor evolution: intertwined hisories. Immunity. 2020 Jan 14;52(1):55-81.
2.Hegde et al. Top 10 Challenges in Cancer Immunotherapy. Immunity. 2020 Jan 14;52(1):17-35.
