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PD-L1 Expression in Colorectal Carcinoma Correlates with the Immune Microenvironment

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Abstract

Introduction/Background

Colorectal carcinoma (CRC) is a common malignancy, with its diverse clinical, pathological, and molecular features. The immune microenvironment of a tumor comprises of interplay between various cells and molecules, and has a significant role in deciding the tumor behavior and overall prognosis. PD-L1 (programmed cell death ligand-1) has been implicated in the regulation of the tumor immune microenvironment (TIME). There is limited data regarding the correlation of PD-L1 expression with immune cell profile in CRCs, especially in the Indian setting. The study aimed to assess the PD-L1 expression in CRC tumor cells and its association with TIME, mismatch repair (MMR), and various other clinicopathological parameters.

Methods

This is a hospital-based, cross-sectional observational study. PD-L1 expression was assessed at the protein level by immunohistochemistry and mRNA level by qRT-PCR. Immune cell markers (CD4, CD8, CD20, FOXP3, and CD163) were interpreted using the ImageJ Fiji platform.

Results

Of the 104 cases, 21% were PD-L1 positive and were more common in right-sided CRCs. PD-L1 positive cases showed significantly higher concentrations of all T-cell subsets (CD4+ , CD8+ , and FOXP3+), CD20+ B-cells, and CD163+ macrophages were noted. No statistical significance was seen between PD-L1 expression with clinical profile, pathological subtype, grade or stage, mismatch repair status (proficient vs deficient), and survival.

Conclusions

The present study showed a relatively lower frequency of PD-L1 in CRC from the Eastern Indian cohort. The immune cell concentration in the present study was calculated using image analysis-based objectivised methods. Significant correlation of PD-L1 expression in tumor cells with the tumor-infiltrating immune cells indicated its crucial role in the pathobiology of CRC especially by regulating the TIME. Considering the therapeutic implication of PD-L1 in various malignancies, it may be one of the crucial therapeutic targets in a proportion of cases.

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Data Availability

The master data sheet used to arrive at the conclusions of the study is available with the corresponding author, and the same may be made available, upon reasonable request.

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.

    Article  PubMed  Google Scholar 

  2. Sinha R, Doval DC, Hussain S, Kumar K, Singh S, Basir SF, Bharadwaj M. Lifestyle and sporadic colorectal cancer in India. Asian Pac J Cancer Prev. 2015;16(17):7683–8.

    Article  PubMed  Google Scholar 

  3. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. N Engl J Med. 2009;361(25):2449–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Müller MF, Ibrahim AE, Arends MJ. Molecular pathological classification of colorectal cancer. Virchows Arch. 2016;469:125–34.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Akiyama M, Matsuda Y, Arai T, Saeki H. PD-L1 expression in malignant melanomas of the skin and gastrointestinal tract. Oncol Lett. 2020;19(3):2481–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Yuan C, Liu Z, Yu Q, Wang X, Bian M, Yu Z, Yu J. Expression of PD-1/PD-L1 in primary breast tumours and metastatic axillary lymph nodes and its correlation with clinicopathological parameters. Sci Rep. 2019;9(1):14356.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Pawelczyk K, Piotrowska A, Ciesielska U, Jablonska K, Gletzel-Plucinska N, Grzegrzolka J, et al. Role of PD-L1 expression in non-small cell lung cancer and their prognostic significance according to clinicopathological factors and diagnostic markers. Int J Mol Sci. 2019;20(4):824.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu X, Choi MG, Kim K, Kim KM, Kim ST, Park SH, Cristescu R, Peter S, Lee J. High PD-L1 expression in gastric cancer (GC) patients and correlation with molecular features. Pathol Res Pract. 2020;216(4): 152881.

    Article  CAS  PubMed  Google Scholar 

  10. Srivastava P, Husain N, Shukla S, Chauhan S, Pandey A, Masood S. PD-L1 Expression in colorectal carcinoma and its correlation with clinicopathological parameters, microsatellite instability and BRAF mutation. Indian J Pathol Microbiol. 2021;64(3):490–6.

    Article  PubMed  Google Scholar 

  11. Shan T, Chen S, Wu T, Yang Y, Li S, Chen X. PD-L1 expression in colon cancer and its relationship with clinical prognosis. Int J Clin Exp Pathol. 2019;12(5):1764–9 Int J Clin Exp Pathol. 2022;15(3):155–156.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Gupta M, Manjari M, Kaur H. PD-L1 Expression in colorectal carcinoma: immunohistochemical study. Annals of Pathology and Laboratory Medicine. 2020;7:A275-281.

    Article  Google Scholar 

  13. Salemme V, Centonze G, Cavallo F, Defilippi P, Conti L. The crosstalk between tumor cells and the immune microenvironment in breast cancer: implications for immunotherapy. Front Oncol. 2021;11: 610303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Soldevilla B, Carretero-Puche C, Gomez-Lopez G, Al-Shahrour F, Riesco MC, Gil-Calderon B, et al. The correlation between immune subtypes and consensus molecular subtypes in colorectal cancer identifies novel tumour microenvironment profiles, with prognostic and therapeutic implications. Eur J Cancer. 2019;123:118–29.

    Article  CAS  PubMed  Google Scholar 

  15. Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24(5):541–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jiang X, Wang J, Deng X, Xiong F, Ge J, Xiang B, et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Mol Cancer. 2019;18(1):1–7.

    Article  CAS  Google Scholar 

  17. Scognamiglio T, Chen YT. Beyond the percentages of PD-L1-positive tumor cells: induced versus constitutive PD-L1 expression in primary and metastatic head and neck squamous cell carcinoma. Head Neck Pathol. 2018;12(2):221–9.

    Article  PubMed  Google Scholar 

  18. Lin G, Fan X, Zhu W, Huang C, Zhuang W, Xu H, et al. Prognostic significance of PD-L1 expression and tumor infiltrating lymphocyte in surgically resectable non-small cell lung cancer. Oncotarget. 2017;8(48):83986.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Mastracci L, Grillo F, Parente P, Gullo I, Campora M, Angerilli V, et al. PD-L1 evaluation in the gastrointestinal tract: from biological rationale to its clinical application. Pathologica. 2022;114(5):352–64.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zlobec I, Steele R, Terracciano L, Jass JR, Lugli A. Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer. J Clin Pathol. 2007;60:1112–6.

    Article  PubMed  Google Scholar 

  21. Agrawal L, Engel KB, Greytak SR, Moore HM. Understanding preanalytical variables and their effects on clinical biomarkers of oncology and immunotherapy. Semin Cancer Biol. 2018;52(Pt 2):26–38.

    Article  CAS  PubMed  Google Scholar 

  22. Huang CY, Wang Y, Luo GY, Han F, Li YQ, Zhou ZG, et al. Relationship between PD-L1 expression and CD8+ T-cell immune responses in hepatocellular carcinoma. J Immunother. 2017;40(9):323–33.

    Article  CAS  PubMed  Google Scholar 

  23. Bai J, Chen H, Bai X. Relationship between microsatellite status and immune microenvironment of colorectal cancer and its application to diagnosis and treatment. J Clin Lab Anal. 2021;35(6): e23810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Deng M, Li SH, Fu X, Yan XP, Chen J, Qiu YD, Guo RP. Relationship between PD-L1 expression, CD8+ T-cell infiltration and prognosis in intrahepatic cholangiocarcinoma patients. Cancer Cell Int. 2021;21(1):371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Que Y, Xiao W, Guan YX, Liang Y, Yan SM, Chen HY, et al. PD-L1 expression is associated with FOXP3+ regulatory T-cell infiltration of soft tissue sarcoma and poor patient prognosis. J Cancer. 2017;8(11):2018–25.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sumitomo R, Hirai T, Fujita M, Murakami H, Otake Y, Huang CL. PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer. Lung Cancer. 2019;136:136–44.

    Article  PubMed  Google Scholar 

  27. Arias-Pulido H, Cimino-Mathews A, Chaher N, Qualls C, Joste N, Colpaert C, Marotti JD, Foisey M, Prossnitz ER, Emens LA, Fiering S. The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome. Breast Cancer Res Treat. 2018;171(2):273–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Guo G, Wang Y, Zhou Y, Quan Q, Zhang Y, Wang H, Zhang B, Xia L. Immune cell concentrations among the primary tumor microenvironment in colorectal cancer patients predicted by clinicopathologic characteristics and blood indexes. J Immunother Cancer. 2019;7(1):179.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Takasu C, Nishi M, Yoshikawa K, Tokunaga T, Kashihara H, Yoshimoto T, Shimada M. Impact of sidedness of colorectal cancer on tumor immunity. PLoS ONE. 2020;15(10): e0240408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Valentini AM, Di Pinto F, Cariola F, Guerra V, Giannelli G, Caruso ML, Pirrelli M. PD-L1 expression in colorectal cancer defines three subsets of tumor immune microenvironments. Oncotarget. 2018;9(9):8584–96.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Chen Y, Liu Q, Chen Z, Wang Y, Yang W, Hu Y, Han W, Zeng H, Ma H, Dai J, Zhang H. PD-L1 expression and tumor mutational burden status for prediction of response to chemotherapy and targeted therapy in non-small cell lung cancer. J Exp Clin Cancer Res. 2019;38(1):193.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

I would like to express my sincere gratitude towards all my teachers and colleagues from All India Institute of Medical Sciences, Bhubaneswar, for their mental support during the study. I would like to express my sincere gratitude to Dr. Mukund Namdev Sable, Additional Professor, for providing the kits for mRNA analysis, and Dr. Kirtal Hansdah and Dr. Swetasmita Mishra, the scientists at the molecular lab, and Mr. Samiur Rahman, for the technical aspects. My sincere gratitude towards all the technical staff of the Histopathology Division of the Department of Pathology, AIIMS Bhubaneswar, for their help with all the technical works related to the study, and to the participants of the study. I would acknowledge the creators of the ImageJ (Fiji) software, which is made available free of cost, without which this study would not have been possible.

Author information

Authors and Affiliations

  1. Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

    Mohammed Shahin, Susama Patra & Suvendu Purkait

  2. Department of Surgical Oncology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

    Madhabananda Kar

  3. Department of Radiation Oncology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

    Saroj Kumar Das Majumdar

  4. Department of General Surgery, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

    Tushar Subhadarshan Mishra

  5. Department of Medical Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

    Subash Chandra Samal & Hemanta Kumar Nayak

Authors
  1. Mohammed Shahin
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Contributions

Prefix

Author name

Name abbreviation

Dr.

Mohammed Shahin

MS

Dr.

Susama Patra

SP

Dr.

Suvendu Purkait

SuP

Dr.

Madhabananda Kar

MK

Dr.

Saroj Kumar Das Majumdar

SKM

Dr.

Tushar Subhadarshan Mishra

TSM

Dr.

Subash Chandra Samal

SCS

Dr.

Hemanta Kumar Nayak

HKN

• All the authors contributed to the study’s conception and design.

• Material preparation, data collection, and analysis were performed by Mohammed Shahin, Susama Patra, and Suvendu Purkait.

• Case management data and specimens were provided by Madhabananda Kar, Saroj Kumar Das Majumdar, Tushar Subhadarshan Mishra, Subash Chandra Samal, and Hemanta Kumar Nayak.

• Case follow-up data were provided by Madhabananda Kar and Saroj Kumar Das Majumdar.

• The first draft of the manuscript was written by Mohammed Shahin, and initially assessed by Susama Patra and Suvendu Purkait.

• Histopathological evaluation and IHC interpretation were done by Mohammed Shahin, Susama Patra, and Suvendu Purkait.

• The master chart was prepared by Mohammed Shahin and statistical analysis was performed by Suvendu Purkait

• All other previous versions were commented upon, and approved by all the authors.

Corresponding author

Correspondence to Susama Patra.

Ethics declarations

Ethics Approval

Ethical approval has been taken from the AIIMS Bhubaneswar Institutional Ethics Committee in February 2020.

Consent to Participate

Informed consent was obtained from all the individual participants included in the study, before their routine diagnostic evaluation and surgical procedure.

Consent to Publish

The authors declare that the participants have provided consent for the publication of images. However, only images of the histopathology slides, IHCs, and ImageJ were included in the study, and duly acknowledged.

Competing Interests

The authors declare no competing interests.

Credits

This paper was presented at the Indian Association of Pathologists and Microbiologists Annual Conference APCON 2022, held in Bengaluru, India, in December 2022, in the “Best Award Paper” category.

The initial abstract of the study was published in the Indian Journal of Pathology and Microbiology. 65(Suppl 2): S1, November 2022.

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Shahin, M., Patra, S., Purkait, S. et al. PD-L1 Expression in Colorectal Carcinoma Correlates with the Immune Microenvironment. J Gastrointest Canc (2024). https://doi.org/10.1007/s12029-024-01049-z

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