Peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms

Our plain-English summary of Peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms, by H. Hu, J. Zhao, J. Yuan, et al (BMC Cancer, 2023).

The study

• Authors: H. Hu, J. Zhao, J. Yuan, M. Zhang
• Journal: BMC Cancer
• Published: 2023;23(1):287
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: Programmed death-1 (PD-1) and T cell immunoglobulin and mucin-domain-containing molecule 3(Tim-3) may be used as the biomarkers for the therapy in patients with peritoneal neoplasms. In the current study, the differential percentages of peripheral PD-1 and Tim-3 are explored to investigate whether to associate with primary sites and pathological types of patients with peritoneal neoplasms or not. We also investigated the frequencies of PD-1 and Tim-3 on circulating Lymphocytes, CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells if would correlate with the progression-free survival of peritoneal neoplasms patients.

Methods: 115 patients with peritoneal neoplasms were recruited, subjected to multicolor flow cytometric analyses of the percentages of PD-1 and Tim-3 receptors of circulating Lymphocytes, CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells. The peritoneal neoplasms patients were divided into primary group and secondary group depending on whether the tumor had primary focus and limited to peritoneal tumor or not. Then all the patients were regrouped by the pathological types of neoplasms (adenocarcinoma, mesothelioma, and pseudomyxoma). The secondary peritoneal neoplasms group was divided into the different primary site groups (colon, gastric, gynecology). This study also enrolled 38 cases of normal volunteers. The above markers were explored by flow cytometer, to find the differential levels in peritoneal neoplasms patients compared with normal group in peripheral blood.

Results: Higher levels of CD4 + T lymphocytes, CD8 + T lymphocytes, CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells, CD3 + CD4 + PD-1 + T cells, CD3 + CD8 + PD-1 + T cells and CD45 + Tim-3 + lymphocytes were found in peritoneal neoplasms group than normal control (the p value was respectively 0.004, 0.047, 0.046, 0.044, 0.014, 0.038 and 0.017). Compared with primary peritoneal neoplasms group, the percentages of CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells, and CD3 + CD4 + PD-1 + T cells were increased in the secondary peritoneal neoplasms group (the p value was respectively 0.010, 0.044, and 0.040), while PD-1 did not correlate with the primary sites in secondary group (P > 0.05). Tim-3 had no statistical differences in primary peritoneal neoplasms group compared with secondary group (p > 0.05), but CD45 + Tim-3+% lymphocytes, CD3 + Tim-3+%T cells, and CD3 + CD4 + Tim-3 + T cells were associated with different secondary sites of peritoneal neoplasms (p < 0.05). In the different pathological type groups, the percentages of CD45 + PD-1 + lymphocytes, CD3 + PD-1 + T cells presented the higher levels in adenocarcinoma group compared with mesothelioma group (p = 0.048, p = 0.045). The frequencies of CD45 + PD-1 + lymphocytes and CD3 + PD-1 + T cells in peripheral blood were associated with progression-free survival (PFS).

Conclusions: Our work uncovers peripheral PD-1 and Tim-3 percentages are associated with primary sites and pathological types of peritoneal neoplasms. Those findings might provide important assessment to predict peritoneal neoplasms patients' immunotherapy responses.

© 2023. The Author(s).

In plain English

This study, from Beijing Shijitan Hospital in China, did not look at asbestos exposure. It measured two immune 'checkpoint' proteins, PD-1 and Tim-3, on white blood cells. Blood came from 115 patients with tumours of the peritoneum (the lining of the abdomen), enrolled April 2021 to May 2022, and from 38 healthy volunteers. Ten patients had mesothelioma and 70 had adenocarcinoma. Patients had higher percentages than volunteers of several PD-1-carrying cell types and of one Tim-3-carrying type. Patients whose tumours had spread from another organ had higher percentages of PD-1-carrying lymphocytes, T cells and CD4 T cells than those whose tumours began in the peritoneum. PD-1-carrying CD8 T cells did not differ significantly (p = 0.112). Two PD-1 measures were higher in the adenocarcinoma group than in the mesothelioma group, for example 24.21% versus 18.62% of lymphocytes (p = 0.045). Patients with high levels of these two measures had shorter median progression-free survival, for example 2.6 versus 8.3 months. The authors concluded that PD-1 and Tim-3 percentages in blood were associated with where the tumours started and what type they were. They noted that the study was small.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Observational laboratory study: flow cytometry of blood samples, comparing patient groups with each other and with healthy controls, plus a progression-free survival analysis
• Who was studied: 115 patients with peritoneal neoplasms at Beijing Shijitan Hospital (Capital Medical University), enrolled April 2021 to May 2022. There were 23 primary and 92 secondary cases. By tumour type: 70 adenocarcinoma, 10 mesothelioma, 7 pseudomyxoma, and others. The study also included 38 healthy gender- and age-matched controls.
• Exposure: No asbestos or other fiber exposure was studied or reported. The factors measured were the percentages of blood lymphocytes and T cells carrying PD-1 and Tim-3.
• Main results:
  • Compared with healthy controls, patients had higher percentages of PD-1-positive lymphocytes, CD3+ T cells, CD4+ T cells and CD8+ T cells (p = 0.046, 0.044, 0.014 and 0.038).
  • CD8+ T cells carrying both PD-1 and Tim-3 were higher in the healthy control group than in patients.
  • Three PD-1 measures (CD45+ PD-1+ lymphocytes, CD3+ PD-1+ T cells and CD3+ CD4+ PD-1+ T cells) were higher in the secondary peritoneal neoplasm group than in the primary group (p = 0.010, 0.044 and 0.040).
  • PD-1 on CD3+ CD8+ T cells did not differ between the secondary and primary groups (p = 0.112).
  • Tim-3 measures did not differ significantly between the primary and secondary groups (p = 0.460, 0.158, 0.381 and 0.309).
  • Within the secondary group, CD45+ Tim-3+ lymphocytes were higher in colon-origin patients than in gynecologic-origin patients (6.26% vs. 9.14%; p = 0.041).
  • In the secondary group, CD3+ Tim-3+ T cells were higher in gastric-origin patients (2.52%) than in colon-origin patients (1.50%; p = 0.048) and gynecologic-origin patients (1.22%; p = 0.021).
  • Compared with the mesothelioma group, the adenocarcinoma group had higher CD45+ PD-1+ lymphocytes (18.62% vs. 24.21%; p = 0.045) and CD3+ PD-1+ T cells (19.83% vs. 23.83%; p = 0.048).
  • Tim-3 levels did not differ among the adenocarcinoma, mesothelioma and pseudomyxoma groups.
  • Median progression-free survival was 2.6 months with high CD45+ PD-1+ lymphocyte levels versus 8.3 months with low levels (p = 0.007). Groups were split at the median.
  • Median progression-free survival was 3.2 months with high CD3+ PD-1+ T cell levels versus 13.1 months with low levels (p = 0.004).
  • Tim-3 levels showed no effect on progression-free survival (p greater than 0.05).
• The authors' conclusion: The authors concluded that blood PD-1 and Tim-3 levels were associated with the primary sites and pathological types of peritoneal neoplasms. They suggested these might serve as candidate biomarkers for future immunotherapy.
• Limitations the authors state:
  • Small sample size.
  • The authors said that, because of the limited sample size, the adenocarcinoma versus mesothelioma differences were not obvious.
  • Only flow cytometry was used; the authors said other methods were needed.
  • The molecular mechanism was not studied.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Neoplasm, Biomarker, Progression-Free Survival, Adenocarcinoma, Mesothelioma, Immunotherapy.

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