Tumor Microenvironment Can Promote Cancer Cell Invasion and Foster Immune Suppression

Rui Gao

doi:10.62051/t3xjpc97

Authors

Rui Gao

DOI:

https://doi.org/10.62051/t3xjpc97

Keywords:

Tumor microenvironment, immune cells, tumor cells, stiffness in tumor microenvironment, cell tension force, extracellular matrix.

Abstract

Immunotherapy against tumors is an emerging field and it is gaining more attention. However, the efficiency of immunotherapy can be hindered by the complexity of the tumor microenvironment. In this paper, the mechanisms by which tumor microenvironment affects immune cells cytotoxicity and how it might suggest new treatment regimes were discussed. In addition, several new in vitro experiments were listed that point to new directions of supplementary treatments to enhance immunotherapy.

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References

[1] C. Wild, E. Weiderpass, and B. Stewart, Eds., World Cancer Report: Cancer Research for Cancer Prevention., vol. 2020. Lyon, France: International Agency for Reseach on Cancer. [Online]. Available: http://publications.iarc.fr/586

[2] A. B. Mariotto, L. Enewold, J. Zhao, C. A. Zeruto, and K. R. Yabroff, “Medical Care Costs Associated with Cancer Survivorship in the United States,” Cancer Epidemiol. Biomarkers Prev., vol. 29, no. 7, pp. 1304–1312, Jul. 2020, doi: 10.1158/1055-9965.EPI-19-1534.

[3] N. Gegechkori, L. Haines, and J. J. Lin, “Long-Term and Latent Side Effects of Specific Cancer Types,” Med. Clin. North Am., vol. 101, no. 6, pp. 1053–1073, Nov. 2017, doi: 10.1016/j.mcna.2017.06.003.

[4] P. Dobosz and T. Dzieciątkowski, “The Intriguing History of Cancer Immunotherapy,” Front. Immunol., vol. 10, p. 2965, Dec. 2019, doi: 10.3389/fimmu.2019.02965.

[5] O. J. Finn, “A Believer’s Overview of Cancer Immunosurveillance and Immunotherapy,” J. Immunol., vol. 200, no. 2, pp. 385–391, Jan. 2018, doi: 10.4049/jimmunol.1701302.

[6] G. Kroemer, T. A. Chan, A. M. M. Eggermont, and L. Galluzzi, “Immunosurveillance in clinical cancer management,” CA. Cancer J. Clin., vol. 74, no. 2, pp. 187–202, Mar. 2024, doi: 10.3322/caac.21818.

[7] H. Raskov, A. Orhan, J. P. Christensen, and I. Gögenur, “Cytotoxic CD8+ T cells in cancer and cancer immunotherapy,” Br. J. Cancer, vol. 124, no. 2, pp. 359–367, Jan. 2021, doi: 10.1038/s41416-020-01048-4.

[8] B. Wang, J. Pei, S. Xu, J. Liu, and J. Yu, “Recent advances in mRNA cancer vaccines: meeting challenges and embracing opportunities,” Front. Immunol., vol. 14, p. 1246682, Sep. 2023, doi: 10.3389/fimmu.2023.1246682.

[9] N. Cruz-Reyes and D. C. Radisky, “Inflammation, Infiltration, and Evasion—Tumor Promotion in the Aging Breast,” Cancers, vol. 15, no. 6, p. 1836, Mar. 2023, doi: 10.3390/cancers15061836.

[10] A. A. Wu, V. Drake, H.-S. Huang, S. Chiu, and L. Zheng, “Reprogramming the tumor microenvironment: tumor-induced immunosuppressive factors paralyze T cells,” OncoImmunology, vol. 4, no. 7, p. e1016700, Jul. 2015, doi: 10.1080/2162402X.2015.1016700.

[11] S. L. Topalian, C. G. Drake, and D. M. Pardoll, “Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy,” Cancer Cell, vol. 27, no. 4, pp. 450–461, Apr. 2015, doi: 10.1016/j.ccell.2015.03.001.

[12] R. Kalluri and R. A. Weinberg, “The basics of epithelial-mesenchymal transition,” J. Clin. Invest., vol. 119, no. 6, pp. 1420–1428, Jun. 2009, doi: 10.1172/JCI39104.

[13] J. J. Li, J. Y. Tsang, and G. M. Tse, “Tumor Microenvironment in Breast Cancer—Updates on Therapeutic Implications and Pathologic Assessment,” Cancers, vol. 13, no. 16, p. 4233, Aug. 2021, doi: 10.3390/cancers13164233.

[14] J. Li, D. Chen, and M. Shen, “Tumor Microenvironment Shapes Colorectal Cancer Progression, Metastasis, and Treatment Responses,” Front. Med., vol. 9, p. 869010, Mar. 2022, doi: 10.3389/fmed.2022.869010.

[15] Y. Yang, Y. Yang, J. Yang, X. Zhao, and X. Wei, “Tumor Microenvironment in Ovarian Cancer: Function and Therapeutic Strategy,” Front. Cell Dev. Biol., vol. 8, p. 758, Aug. 2020, doi: 10.3389/fcell.2020.00758.

[16] T. Murakami, Y. Hiroshima, R. Matsuyama, Y. Homma, R. M. Hoffman, and I. Endo, “Role of the tumor microenvironment in pancreatic cancer,” Ann. Gastroenterol. Surg., vol. 3, no. 2, pp. 130–137, Mar. 2019, doi: 10.1002/ags3.12225.

[17] H. F. Bahmad et al., “Tumor Microenvironment in Prostate Cancer: Toward Identification of Novel Molecular Biomarkers for Diagnosis, Prognosis, and Therapy Development,” Front. Genet., vol. 12, p. 652747, Mar. 2021, doi: 10.3389/fgene.2021.652747.

[18] J. W. Mier, “The tumor microenvironment in renal cell cancer,” Curr. Opin. Oncol., vol. 31, no. 3, pp. 194–199, May 2019, doi: 10.1097/CCO.0000000000000512.

[19] E. E. Graves, A. Maity, and Q.-T. Le, “The Tumor Microenvironment in Non–Small-Cell Lung Cancer,” Semin. Radiat. Oncol., vol. 20, no. 3, pp. 156–163, Jul. 2010, doi: 10.1016/j.semradonc.2010.01.003.

[20] B. C. Özdemir et al., “Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival,” Cancer Cell, vol. 25, no. 6, pp. 719–734, Jun. 2014, doi: 10.1016/j.ccr.2014.04.005.

[21] Y. Ino et al., “Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer,” Br. J. Cancer, vol. 108, no. 4, pp. 914–923, Mar. 2013, doi: 10.1038/bjc.2013.32.

[22] E. Cortes et al., “GPER is a mechanoregulator of pancreatic stellate cells and the tumor microenvironment,” EMBO Rep., vol. 20, no. 1, p. e46556, Jan. 2019, doi: 10.15252/embr.201846556.

[23] S. K. Kim and S. W. Cho, “The Evasion Mechanisms of Cancer Immunity and Drug Intervention in the Tumor Microenvironment,” Front. Pharmacol., vol. 13, p. 868695, May 2022, doi: 10.3389/fphar.2022.868695.

[24] D. Lachowski et al., “Substrate Rigidity Controls Activation and Durotaxis in Pancreatic Stellate Cells,” Sci. Rep., vol. 7, no. 1, p. 2506, May 2017, doi: 10.1038/s41598-017-02689-x.

[25] C. Matellan et al., “Retinoic acid receptor β modulates mechanosensing and invasion in pancreatic cancer cells via myosin light chain 2,” Oncogenesis, vol. 12, no. 1, p. 23, May 2023, doi: 10.1038/s41389-023-00467-1.

[26] M. Sarper, E. Cortes, T. J. Lieberthal, and A. Del Río Hernández, “ATRA modulates mechanical activation of TGF-β by pancreatic stellate cells,” Sci. Rep., vol. 6, no. 1, p. 27639, Jul. 2016, doi: 10.1038/srep27639.

[27] A. J. Rice et al., “Matrix stiffness induces epithelial–mesenchymal transition and promotes chemoresistance in pancreatic cancer cells,” Oncogenesis, vol. 6, no. 7, pp. e352–e352, Jul. 2017, doi: 10.1038/oncsis.2017.54.

[28] R. Basu et al., “Cytotoxic T Cells Use Mechanical Force to Potentiate Target Cell Killing,” Cell, vol. 165, no. 1, pp. 100–110, Mar. 2016, doi: 10.1016/j.cell.2016.01.021.

[29] M. Tello-Lafoz et al., “Cytotoxic lymphocytes target characteristic biophysical vulnerabilities in cancer,” Immunity, vol. 54, no. 5, pp. 1037-1054.e7, May 2021, doi: 10.1016/j.immuni.2021.02.020.

[30] K. Lei et al., “Cancer-cell stiffening via cholesterol depletion enhances adoptive T-cell immunotherapy,” Nat. Biomed. Eng., vol. 5, no. 12, pp. 1411–1425, Dec. 2021, doi: 10.1038/s41551-021-00826-6.