Combined ROS-related therapy improves the efficacy of multipleneoantigen vaccines against LUAD
DOI:
https://doi.org/10.61173/sw4w4b51Keywords:
Lung Adenocarcinoma, Multiple neoantigen vaccines, tumor microenvironment, reactive oxygen species, Intratumoral GSH depletion, TME ROS scavengingAbstract
Lung adenocarcinoma (LUAD) is classified as Non-Small-Cell Lung Cancer (NSCLC), one of the most malignant
cancers due to its poor prognosis and fast progression. Its resistance to chemotherapy, immunosuppressive tumor
microenvironment (TME), and frequent immune evasion also impose enormous obstacles in treating LUAD. However,
previous research found that these tumor cells resistant to chemotherapies commonly increase their production of
intracellular reactive oxygen species (ROS) due to high mitochondria activity. Antioxidants like glutathione (GSH)
are also highly produced to maintain their redox homeostasis. Therefore, the depletion of antioxidants which can lead
to intratumoral accumulation of ROS to cytotoxic levels, provides a new therapeutic target. Besides, the high level
of extracellular ROS also significantly contributes to the immunosuppressive characteristic of TME, which exhausts
activated T cells. This work provides the framework for a novel combinational therapy based on a multiple-neoantigen
vaccine to avoid immune evasion. Two types of nanoparticles further boost the vaccine’s efficacy against tumors, one
depleting intratumoral GSH and scavenging extracellular ROS. Anticipated results are shown from various aspects,
hoping the innovative treatment can effectively improve the survival rate with few side effects.
References
[1] World Health Organization. (2022). Cancer today. Global Cancer Observatory. https://gco.iarc.fr/today/home, accessed on Aug 4, 2022
[2] Beadsmoore, C. J., & Screaton, N. J. (2003). Classification, staging and prognosis of lung cancer. European Journal of Radiology, 45(1), 8–17. https://doi.org/10.1016/s0720- 048x(02)00287-5
[3] Centers for Disease Control and Prevention. (2022). Lung cancer statistics. https://www.cdc.gov/cancer/lung/statistics/, accessed on Aug 4, 2022
[4] Yousem, S. A. (2012). Role of molecular studies in the diagnosis of lung adenocarcinoma. Modern Pathology, 25(S1). https://doi.org/10.1038/modpathol.2011.156
[5] Wangpaichitr, M., Wu, C., Li, Y. Y., Nguyen, D. J. M., Kandemir, H., Shah, S., Chen, S., Feun, L. G., Prince, J. S., Kuo, M. T., & Savaraj, N. (2017). Exploiting Ros and metabolic differences to kill cisplatin resistant lung cancer. Oncotarget, 8(30), 49275–49292. https://doi.org/10.18632/oncotarget.17568
[6] Rosenthal, R., Cadieux, E. L., Salgado, R., Bakir, M. A., Moore, D. A., Hiley, C. T., Lund, T., Tanić, M., Reading, J. L., Joshi, K., Henry, J. Y., Ghorani, E., Wilson, G. A., Birkbak, N. J., Jamal-Hanjani, M., Veeriah, S., Szallasi, Z., Loi, S., & Swanton, C. (2019). Neoantigen-directed immune escape in lung cancer evolution. Nature, 567(7749), 479-485. https://doi.org/10.1038/ s41586-019-1032-7
[7] Ye, M., Han, Y., Tang, J., Piao, Y., Liu, X., Zhou, Z., Gao, J., Rao, J., & Shen, Y. (2017). A tumor-specific cascade amplification drug release nanoparticle for overcoming multidrug resistance in cancers. Advanced Materials, 29(38), 1702342. https://doi.org/10.1002/adma.201702342
[8] Yadav, M., Jhunjhunwala, S., Phung, Q. T., Lupardus, P., Tanguay, J., Bumbaca, S., Franci, C., Cheung, T. K., Fritsche, J., Weinschenk, T., Modrusan, Z., Mellman, I., Lill, J. R., & Delamarre, L. (2014). Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature, 515(7528), 572-576. https://doi.org/10.1038/nature14001
[9] Chen, P., Fang, Q., Chen, D., & Chen, H. (2021). Neoantigen vaccine: An emerging immunotherapy for hepatocellular carcinoma. World Journal of Gastrointestinal Oncology, 13(7), 498-508. https://doi.org/10.4251/wjgo.v13.i7.498
[10] D’Alise, A. M., Leoni, G., Cotugno, G., Troise, F., Langone, F., Fichera, I., De Lucia, M., Avalle, L., Vitale, R., Leuzzi, A., Bignone, V., Di Matteo, E., Tucci, F. G., Poli, V., Lahm, A., Catanese, M. T., Folgori, A., Colloca, S., Nicosia, A., … Scarselli, E. (2019). Adenoviral vaccine targeting multiple neoantigens as strategy to eradicate large tumors combined with checkpoint blockade. Nature Communications, 10(1). https://doi. org/10.1038/s41467-019-10594-2
[11] Veatch, J. R., Singhi, N., Srivastava, S., Szeto, J. L., Jesernig, B., Stull, S. M., Fitzgibbon, M., Sarvothama, M., Yechan-Gunja, S., James, S. E., & Riddell, S. R. (2021). A therapeutic cancer vaccine delivers antigens and adjuvants to lymphoid tissues using genetically modified T cells. Journal of Clinical Investigation, 131(16). https://doi.org/10.1172/ jci144195
[12] Liou, G.-Y., & Storz, P. (2010). Reactive oxygen species in cancer. Free Radical Research, 44(5), 479–496. https://doi. org/10.3109/10715761003667554
[13] Cemerski, S., Cantagrel, A., van Meerwijk, J. P. M., & Romagnoli, P. (2002). Reactive oxygen species differentially affect T cell receptor-signaling pathways*. Journal of Biological Chemistry, 277(22), 19585–19593. https://doi.org/10.1074/jbc. m111451200
[14] Weinberg, F., Ramnath, N., & Nagrath, D. (2019). Reactive oxygen species in the tumor microenvironment: An overview. Cancers, 11(8), 1191. https://doi.org/10.3390/cancers11081191
[15] Chen, X., Song, M., Zhang, B., & Zhang, Y. (2016). Reactive oxygen species regulate T cell immune response in the tumor microenvironment. Oxidative Medicine and Cellular Longevity, 2016, 1–10. https://doi.org/10.1155/2016/1580967
[16] Zhang, Z., Gao, Z., Rajthala, S., Sapkota, D., Dongre, H., Parajuli, H., Suliman, S., Das, R., Li, L., Bindoff, L. A., Costea, D. E., & Liang, X. (2019). Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma associated fibroblasts. Cellular and Molecular Life Sciences, 77(6), 1115–1133. https://doi.org/10.1007/s00018- Dean&Francis 019-03209-y
[17] Nechifor, M., Neagu, T.-M., & Manda, G. (2009). Reactive oxygen species, cancer and anti-cancer therapies. Current Chemical Biology, 3(1), 22–46. https://doi.org/10.2174/2212796 810903010022
[18] Whiteside, T. L. (2008). The tumor microenvironment and its role in promoting tumor growth. Oncogene, 27(45), 5904– 5912. https://doi.org/10.1038/onc.2008.271
[19] Jelic, M. D., Mandic, A. D., Maricic, S. M., & Srdjenovic, B. U. (2021). Oxidative stress and its role in cancer. Journal of Cancer Research and Therapeutics, 17(1), 22. https://doi. org/10.4103/jcrt.jcrt_862_16
[20] Wu, G., Fang, Y.-Z., Yang, S., Lupton, J. R., & Turner, N. D. (2004). Glutathione metabolism and its implications for health. The Journal of Nutrition, 134(3), 489–492. https://doi. org/10.1093/jn/134.3.489
[21] Deng, H., Yang, W., Zhou, Z., Tian, R., Lin, L., Ma, Y., Song, J., & Chen, X. (2020). Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death. Nature Communications, 11(1). https://doi.org/10.1038/s41467- 020-18745-6
[22] Chen, Q., Zhou, J., Chen, Z., Luo, Q., Xu, J., & Song, G. (2019). Tumor-specific expansion of oxidative stress by glutathione depletion and use of a Fenton Nanoagent for enhanced chemodynamic therapy. ACS Applied Materials & Interfaces, 11(34), 30551–30565. https://doi.org/10.1021/ acsami.9b09323
[23] Nolan, K., Verzosa, G., Cleaver, T., Tippimanchai, D., DePledge, L. N., Wang, X., Young, C., Le, A., Doebele, R., Li, H., & Malkoski, S. P. (2020). Development of syngeneic murine cell lines for use in immunocompetent orthotopic lung cancer models. Cancer Cell International, 20(1). https://doi.org/10.1186/ s12935-020-01503-5
Downloads
Published
Issue
Section
License
Copyright (c) 2023 by the authors.
This work is licensed under a Creative Commons Attribution 4.0 International License.
