Immune checkpoint protein and cytokine expression by T lymphocytes in pleural effusion of cancer patients receiving anti–PD-1 therapy

Yuki Ikematsu, Kentaro Tanaka, Toyoshi Yanagihara, Renpeng Liu, Hiroyuki Inoue, Yasuto Yoneshima, keiichi ota, Eiji Iwama, Shohei Takata, Kentaro Hata, Yuriko Takahata, Hiroshi Wataya, Yoichi Nakanishi, Isamu Okamoto

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Objectives: Pleural effusion (PE) occasionally develops in cancer patients during treatment with antibodies to programmed cell death–1 (PD-1) or to its ligand PD-L1 (hereafter, αPD-1 therapy). Such effusion often contains infiltrated mononuclear cells, although the types of immune cell present as well as the outcome of such patients have remained unclear. Materials and methods: We performed a multi-institutional, observational study to examine the clinical outcome of patients who develop PE after the onset of αPD-1 therapy. We compared the immune cell profiles and the immune status of lymphocytes in PE as determined by flow cytometry between nine patients who developed effusion during αPD-1 therapy (αPD-1 group) and 15 patients who developed PE during treatment with other anticancer agents (control group). Results: Most mononuclear cells in PE were lymphocytes in both the αPD-1 and control groups. The frequency of both CD4+ and CD8+ T lymphocytes expressing the immune checkpoint proteins TIM-3 or TIGIT as well as that of CD8+ T lymphocytes expressing PD-L1 were increased in the αPD-1 group compared with the control group. αPD-1 therapy continued for a substantial period after the emergence of PE in six of the nine patients in the αPD-1 group, and the frequency of CD4+ T lymphocytes in PE expressing the immune checkpoint protein LAG-3 or the cytokine interkeukin-17 was lower for these patients than for those who did not receive a sustained treatment benefit. Conclusion: Our results suggest a clinical benefit of continuing αPD-1 therapy in some patients who develop PE. We found that infiltrating T lymphocytes in PE manifest a more exhausted phenotype during αPD-1 therapy than during treatment with other cancer drugs, with subpopulations of these cells characterized by specific immune checkpoint protein and cytokine expression profiles possibly contributing to the antitumor immune response.

Original languageEnglish
Pages (from-to)58-64
Number of pages7
JournalLung Cancer
Publication statusPublished - Dec 2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research


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