Discussion
tumor, CTCL, T cell lymphoma, erythema, pruritus, T cell lymphomas
TUMOR, T CELL LYMPHOMA, PROLIFERATION, ERYTHEMA, LYMPHOMA
The mechanism underlying the progression of T cell lymphoma after anti–PD-1 immunotherapy remains largely unknown. Our study reveals that PD-1 exerted a tumor suppressive role on malignant T cells with constitutive TCR activation; PD-1 blockade therapy ameliorated the inhibitory role of PD-1 signaling on malignant T cells, thereby accelerating the progression of CTCL (Physiologically, PD-1 is upregulated upon TCR engagement, and PD-1 signaling inhibits the proliferation of T cells with TCR signaling activation (Our findings from single-cell transcriptome analyses before and after treatment suggest that the tumor-suppressive mechanisms of PD-1 overlap with physiological PD-1 signaling, consistent with findings from the Studies based on high-throughput sequencing in the past decade have revealed that oncogenic genetic aberrations in components of the T cell activation/NF-κB pathway are hallmarks of T cell lymphomas (In addition, lymphoma hyperprogression should be distinguished from skin flare reaction after anti–PD-1 treatment. In the phase II trial of pembrolizumab in CTCL, 53% of patients with SS experienced marked worsening of erythema and pruritus during treatment (Our work has several limitations. The single-case design of this study makes it challenging to draw an exclusive link between Taken together, the results of our study provide real-world clinical evidence that PD-1 acts as a tumor suppressor for malignant T cells with oncogenic TCR activation. These results highlight the importance of tumor genomic profiling in improving the clinical benefit of anti–PD-1/PD-L1 regimens in patients with T cell lymphomas in the future.