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Prognostic significance of immune checkpoints in the tumour–stromal microenvironment of sebaceous gland carcinoma
  1. Lata Singh1,2,
  2. Mithalesh Kumar Singh1,
  3. Moshahid Alam Rizvi2,
  4. Neelam Pushker3,
  5. Sameer Bakhshi4,
  6. Seema Sen1,
  7. Seema Kashyap1
  1. 1 Ocular Pathology, All India Institute of Medical Sciences, New Delhi, Delhi, India
  2. 2 Biosciences, Jamia Millia Islamia, New Delhi, Delhi, India
  3. 3 Ophthalmology, Dr R P Centre, AIIMS, New Delhi, Delhi, India
  4. 4 Medical Oncology, IRCH, AIIMS, New Delhi, India
  1. Correspondence to Professor Seema Kashyap, Ocular Pathology, All India Institute of Medical Sciences, New Delhi, Delhi, India; seemakashyap65{at}gmail.com; lata.aiims{at}gmail.com

Abstract

Background Immune checkpoint blockade strategies have gained attention in the treatment/prognosis of cancers by targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway alone or in combination with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade and are currently in clinical trials. The present study investigated the expression of the PD-1, PD-L1, CTLA-4, CD4 and CD8 proteins and their prognostic value in the tumour microenvironment of sebaceous gland carcinoma (SGC).

Methods The expression levels of PD-1, PD-L1, CTLA-4, CD4 and CD8 proteins were assessed in 52 cases of SGC by immunohistochemistry and validated by western blotting. mRNA expression was measured by quantitative real-time PCR. Kaplan-Meier curves and Cox proportional hazard models were used to analyse the correlation of protein expression with clinicopathological parameters and disease-free survival.

Results The expression of PD-L1 was found to be higher in tumour cells than in stromal cells. In univariate analysis, the expression of PD-1 in tumour-infiltrating lymphocytes (tPD-1) and PD-L1 in tumour cells was associated with reduced disease-free survival, whereas PD-L1 expression in stromal lymphocyte infiltration (sPD-L1) was associated with the increased survival of patients (p<0.05). However, by multivariate analysis, the expression of tPD-1 was found to be an independent prognostic factor for poor survival.

Conclusion Our study highlights the prognostic outcome of PD-1 and PD-L1 protein expression in cells of tumour–stromal compartments. These results indicate that the PD-1/PD-L1 pathway mediates important interactions within the tumour microenvironment in SGC.

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  • pathology
  • immunology
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Footnotes

  • LS and SK contributed equally.

  • Presented at The present study was presented as a poster presentation at the European Society of Medical Oncology (ESMO) Congress, 19–23 October 2018, in Munich, Germany.

  • Author contributions: LS and MR were responsible for the conception and design of the work. LS, SK and MKS contributed to the acquisition, analysis and interpretation of data for the work. NP provided the tissue samples. SB helped in the follow-up of the patients. SS helped in reviewing the histopathology slides. All authors reviewed and approved the final version of the manuscript.

  • Funding The Department of Science and Technology provided a national postdoctoral fellowship (N-PDF) to Lata Singh to conduct this research.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethical approval Obtained from the Institute’s Ethical Committee, All India Institute of Medical Sciences (Ref. No. IEC-424/RP-6/2016).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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