Comprehensive immune profiling of lung adenocarcinomas reveals four immunosubtypes with plasma cell subtype a negative indicator

Neoplastic cancer cells and cancer stroma (including infiltrating immune cells) determine the biology and prognosis of cancer. Various types of adaptive and innate immune cells are known to infiltrate the cancer stroma. However, the patterns and spatial distribution of immune cell infiltration as well as its association with tumor histology remain poorly understood. To address these issues, we comprehensively analyzed the infiltrating immune cells present in lung adenocarcinoma. The principal types of both adaptive and innate infiltrating immune cells were immunohistochemically evaluated in the predominant histologic components of 111 lung adenocarcinomas. The same analysis was also carried out on 143 samples of histologic subtypes making up more than 20% of tumors. As a result, plasma cells and B cells with interfollicular distribution were almost exclusively observed in invasive histologic subtypes, while an increased number of mast cells were observed in noninvasive histologic subtypes. Cluster analysis revealed four distinct immunosubtypes (CD8, mast cell, macrophage/dendritic cell, and plasma cell subtypes) based on the infiltrating immune cell profiles. These immunosubtypes correlated with histologic subtypes, and univariate and multivariate analyses identified the plasma cell subtype as an independent negative prognostic factor. These plasma cells may be one of the major producers of the immunosuppressive cytokine IL35 in cancer stroma.