Hepatocellular Carcinoma and Immunotherapy

Can anti-PD1/PD-L1 Immunotherapy Promote Macrophage Activity against HCC cells?

Authors

  • Manasi Vegesna Hamilton High School
  • Dr. Jessica Lancaster Mayo Clinic
  • Dr. Ildefonso Alves da Silva Mayo Clinic

DOI:

https://doi.org/10.47611/jsrhs.v12i3.4714

Keywords:

Hepatocelular carcinoma, PD1/PD-L1 antibodies, Macrophages, MHCI/MHCII, Immunosuppression, Anti-tumor activity

Abstract

With over 750,000 new cases identified annually, hepatocellular carcinoma (HCC) continues to be a threat, with current immunotherapies producing ineffective results in a majority of patients. PD1/PD-L1 antibodies have risen as another treatment option, but previous studies have only analyzed these antibodies in the tumor microenvironment. In order to understand how exactly these PD1/PD-L1 blockers affect macrophages and their anti-tumor macrophages, this study isolated the macrophage cells and tumor cells. Two protocols were followed, one with the B16F10 melanoma cell line, in order to determine proper procedures and determine a point of comparison, and one with the R1LWT liver cancer cell line. In the end, the B16F10 cell line responded positively to the PD1/PD-L1 antibodies, with increased MHCI/MHCII activation. On the other hand, the R1LWT cell line reacted oppositely, opening new inquiries into other pathways by which immunosuppression occurs.

Downloads

Download data is not yet available.

Author Biographies

Dr. Jessica Lancaster, Mayo Clinic

Assistant Professor of Immunology at the Department of Immunology and Cancer Biology 

Dr. Ildefonso Alves da Silva, Mayo Clinic

Postdoctoral Research Fellow in Immunology and Cancer Research

References or Bibliography

A, T. (n.d.). Immunology: What cells have a myeloid lineage and how are they identified? Blog.cellsignal.com. https://blog.cellsignal.com/immunology-what-cells-have-a-myeloid-lineage-and-how-are-they-identified

Alsaab, H. O., Sau, S., Alzhrani, R., Tatiparti, K., Bhise, K., Kashaw, S. K., & Iyer, A. K. (2017). PD-1 and PD-L1 Checkpoint Signaling Inhibition for Cancer Immunotherapy: Mechanism, Combinations, and Clinical Outcome. Frontiers in Pharmacology, 8. https://doi.org/10.3389/fphar.2017.00561

Bocanegra, A., Blanco, E., Fernandez-Hinojal, G., Arasanz, H., Chocarro, L., Zuazo, M., Morente, P., Vera, R., Escors, D., & Kochan, G. (2020). PD-L1 in Systemic Immunity: Unraveling Its Contribution to PD-1/PD-L1 Blockade Immunotherapy. International Journal of Molecular Sciences, 21(16), 5918. https://doi.org/10.3390/ijms21165918

Capece, D., Fischietti, M., Verzella, D., Gaggiano, A., Cicciarelli, G., Tessitore, A., Zazzeroni, F., & Alesse, E. (2013). The Inflammatory Microenvironment in Hepatocellular Carcinoma: A Pivotal Role for Tumor-Associated Macrophages. BioMed Research International, 2013, 1–15. https://doi.org/10.1155/2013/187204

Gu, S. S., Zhang, W., Wang, X., Jiang, P., Traugh, N., Li, Z., Meyer, C., Stewig, B., Xie, Y., Bu, X., Manos, M. P., Font-Tello, A., Gjini, E., Lako, A., Lim, K., Conway, J., Tewari, A. K., Zeng, Z., Sahu, A. D., & Tokheim, C. (2021). Therapeutically Increasing MHC-I Expression Potentiates Immune Checkpoint Blockade. Cancer Discovery, 11(6), 1524–1541. https://doi.org/10.1158/2159-8290.cd-20-0812

Hirayama, D., Lida, T., & Nakase, H. (2017). The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis. International Journal of Molecular Sciences, 19(1), 92. https://doi.org/10.3390/ijms19010092

Hu, Z., Ye, L., Xing, Y., Hu, J., & Xi, T. (2018). Combined SEP and anti-PD-L1 antibody produces a synergistic antitumor effect in B16-F10 melanoma-bearing mice. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-017-18641-y

Huang, Y., Ge, W., Zhou, J., Gao, B., Qian, X., & Wang, W. (2021). The Role of Tumor Associated Macrophages in Hepatocellular Carcinoma. Journal of Cancer, 12(5), 1284–1294. https://doi.org/10.7150/jca.51346

Kapanadze, T., Gamrekelashvili, J., Ma, C., Chan, C., Zhao, F., Hewitt, S., Zender, L., Kapoor, V., Felsher, D. W., Manns, M. P., Korangy, F., & Greten, T. F. (2013). Regulation of accumulation and function of myeloid derived suppressor cells in different murine models of hepatocellular carcinoma. Journal of Hepatology, 59(5), 1007–1013. https://doi.org/10.1016/j.jhep.2013.06.010

Kohli, K., Pillarisetty, V. G., & Kim, T. S. (2021). Key chemokines direct migration of immune cells in solid tumors. Cancer Gene Therapy. https://doi.org/10.1038/s41417-021-00303-x

Kuang, D.-M., Zhao, Q., Peng, C., Xu, J., Zhang, J.-P., Wu, C., & Zheng, L. (2009). Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. The Journal of Experimental Medicine, 206(6), 1327–1337. https://doi.org/10.1084/jem.20082173

López-Requena, A., Burrone, O. R., & Cesco-Gaspere, M. (2012). Idiotypes as immunogens: facing the challenge of inducing strong therapeutic immune responses against the variable region of immunoglobulins. Frontiers in Oncology, 2. https://doi.org/10.3389/fonc.2012.00159

Macek Jilkova, Z., Kurma, K., & Decaens, T. (2019). Animal Models of Hepatocellular Carcinoma: The Role of Immune System and Tumor Microenvironment. Cancers, 11(10), 1487. https://doi.org/10.3390/cancers11101487

National Cancer Institute. (2011, February 2). https://www.cancer.gov/publications/dictionaries/cancer-terms/def/adaptive-immunity. Www.cancer.gov. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/adaptive-immunity

Ovchinnikov, A. G., Arefieva, T. I., Potekhina, A. V., Filatova, A. Yu., Ageev, F. T., & Boytsov, S. А. (2020). The Molecular and Cellular Mechanisms Associated with a Microvascular Inflammation in the Pathogenesis of Heart Failure with Preserved Ejection Fraction. Acta Naturae, 12(2), 40–51. https://doi.org/10.32607/actanaturae.10990

Pu, Y., & Ji, Q. (2022). Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.874589

Rock, K. L., Reits, E., & Neefjes, J. (2016). Present Yourself! By MHC Class I and MHC Class II Molecules. Trends in Immunology, 37(11), 724–737. https://doi.org/10.1016/j.it.2016.08.010

Romano, E., Rufo, N., Korf, H., Mathieu, C., Garg, A. D., & Agostinis, P. (2018). BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells. Oncotarget, 9(25). https://doi.org/10.18632/oncotarget.24815

Stout, R. D., Jiang, C., Matta, B., Tietzel, I., Watkins, S. K., & Suttles, J. (2005). Macrophages Sequentially Change Their Functional Phenotype in Response to Changes in Microenvironmental Influences. The Journal of Immunology, 175(1), 342–349. https://doi.org/10.4049/jimmunol.175.1.342

Su, C., Wang, H., Liu, Y., Guo, Q., Zhang, L., Li, J., Zhou, W., Yan, Y., Zhou, X., & Zhang, J. (2020). Adverse Effects of Anti-PD-1/PD-L1 Therapy in Non-small Cell Lung Cancer. Frontiers in Oncology, 10, 554313. https://doi.org/10.3389/fonc.2020.554313

Sun, J.-Y., Zhang, D., Wu, S., Xu, M., Zhou, X., Lu, X.-J., & Ji, J. (2020). Resistance to PD-1/PD-L1 blockade cancer immunotherapy: mechanisms, predictive factors, and future perspectives. Biomarker Research, 8(1). https://doi.org/10.1186/s40364-020-00212-5

Tian, Z., Hou, X., Liu, W., Han, Z., & Wei, L. (2019). Macrophages and hepatocellular carcinoma. Cell & Bioscience, 9(1). https://doi.org/10.1186/s13578-019-0342-7

Wieczorek, M., Abualrous, E. T., Sticht, J., Álvaro-Benito, M., Stolzenberg, S., Noé, F., & Freund, C. (2017). Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation. Frontiers in Immunology, 8. https://doi.org/10.3389/fimmu.2017.00292

Xu, W., Cheng, Y., Guo, Y., Yao, W., & Qian, H. (2022). Targeting tumor associated macrophages in hepatocellular carcinoma. Biochemical Pharmacology, 199, 114990. https://doi.org/10.1016/j.bcp.2022.114990

Yoo, S. Y., Badrinath, N., Woo, H. Y., & Heo, J. (2017). Oncolytic Virus-Based Immunotherapies for Hepatocellular Carcinoma. Mediators of Inflammation, 2017(5198798), 1–12. https://doi.org/10.1155/2017/5198798

Zeng, Z., Yang, B., & Liao, Z. (2020). Current progress and prospect of immune checkpoint inhibitors in hepatocellular carcinoma (Review). Oncology Letters. https://doi.org/10.3892/ol.2020.11909

Zhang, W., Liu, Y., Yan, Z., Yang, H., Sun, W., Yao, Y., Chen, Y., & Jiang, R. (2020). IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma. Journal for ImmunoTherapy of Cancer, 8(1), e000285. https://doi.org/10.1136/jitc-2019-000285

Published

08-31-2023

How to Cite

Vegesna, M., Lancaster, J., & Alves da Silva, I. . (2023). Hepatocellular Carcinoma and Immunotherapy: Can anti-PD1/PD-L1 Immunotherapy Promote Macrophage Activity against HCC cells?. Journal of Student Research, 12(3). https://doi.org/10.47611/jsrhs.v12i3.4714

Issue

Section

HS Research Articles