[The microenvironment and immune status of peripheral T-cell lymphoma: focusing on AITL and ATLL]

Angioimmunoblastic T-cell lymphoma (AITL) originates from follicular helper T cells and shows variable biological and clinical presentations. The survival rate of patients with AITL did not correlate with T-cell clonality, the presence of EBV-infected cells, EBV-DNA copy number, or IgH rearrangements. However, tumor-associated macrophage/M2 macrophages significantly correlated with worse overall survival (OS). Additionally, patients with composite lymphoma with diffuse large B cell lymphoma and AITL showed worse OS. We reported mutations in TET2, DNMT3A, IDH2, and RHOA. TET2 and DNMT3A mutations were identified in both programmed cell death 1 (PD1) + T cells and CD20+ cells. All RHOA and IDH2 mutations were confined to PD1+ T cells, whereas several mutations, including NOTCH1 mutations, were detected only in CD20+ cells. TET2 and DNMT3A mutations may originate in hematopoietic progenitor cells. Adult T-cell leukemia/lymphoma (ATLL) expresses CCR4 and FOXP3 of the regulatory T-cell marker. The p40tax viral protein leads to the transcriptional activation of several genes. In addition, the HTLV-1 basic leucine zipper factor is considered important for T-cell proliferation and oncogenesis. The presence of Tax-specific cytotoxic T lymphocytes is inversely correlated with FOXP3 expression. M2 macrophages were associated with worse clinical prognosis in patients with ATLL. Programmed cell death ligand 1 (PD-L1) expression showed two patterns, namely neoplastic PD-L1 (nPD-L1) and microenvironmental PD-L1 (miPD-L1). Patients with nPD-L1-positive ATLL cells had inferior OS, whereas those with miPD-L1-positive ATLL cells had superior OS. Patients with a HLA+ beta2M+ phenotype had significantly better prognosis, and those with a HLAm+ beta2Mm+ miPD-L1high phenotype demonstrated the most favorable prognosis. Thus, our study demonstrated that understanding the microenvironment is critical in discerning the clinicopathological features of peripheral T-cell lymphoma.