Abstract Aim Peripheral T‐cell lymphoma not otherwise specified (PTCL‐NOS) is a heterogeneous disease that can be classified into the PTCL‐TBX21 and PTCL‐GATA3 subtypes. Methods In this study, we compared the clinicopathological features of PTCL‐NOS in a Japanese cohort, classified using an IHC algorithm. Results One hundred patients with PTCL‐NOS were categorized as having PTCL‐TBX21 (n = 55), PTCL‐GATA3 (n = 24), or PTCL‐unclassified (n = 21). When comparing PTCL‐TBX21 and PTCL‐GATA3, PTCL‐TBX21 showed significantly lower CD4 positivity (p = 0.047), lower counts of high endothelial venules (p = 0.032), and a tendency for a better response to initial treatment (p = 0.088). Gene expression analysis using the nCounter system showed higher expression of tumor immunity‐related genes, such as PD‐L1, LAG3, and IDO1, in PTCL‐TBX21 than in PTCL‐GATA3. PTCL‐GATA3 had significantly worse overall survival (OS) than those with PTCL‐TBX21 (p = 0.047), although a similar tendency was observed for progression‐free survival (PFS) (p = 0.064). PTCL‐GATA3 was a prognostic factor for OS in univariate analysis (HR 2.02; 95% CI, 1.09–3.77; p = 0.027), although multivariate analysis did not show significance (HR 2.07; 95% CI, 0.93–4.61; p = 0.074). In the PFS analysis, PTCL‐GATA3 was an independent prognostic factor by univariate analysis (HR 1.96; 95% CI, 1.08–3.56; p = 0.027) and multivariate analysis (HR 2.34; 95% CI, 1.07–5.11; p = 0.032). Conclusion The classification of PTCL‐NOS into PTCL‐TBX21 and PTCL‐GATA3 is useful for predicting the prognosis of Japanese patients and stratifying the administration of tumor immune checkpoint inhibitors in clinical practice.
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