How immunotherapy and targeted therapy are changing gastrointestinal cancer treatment
Main Article Content
Abstract
Tumor angiogenesis is a critical process that enables the progression and metastasis of solid tumors, including gastrointestinal cancer. The microenvironment of gastric cancer is characterized by hypoxia, which suppresses the ability of the immune system to fight cancer. Existing treatment regimens do not address this complication and consequently do not result in objective tumor shrinkage. Accordingly, new treatment strategies are urgently needed for gastric cancer. Targeted therapies and immunotherapy for some patients with advanced gastrointestinal cancer are new approaches to this difficult-to-treat cancer, which has not benefited from substantial therapeutic advances in recent years. We propose a new treatment strategy based on anti-angiogenic therapy for gastric cancer. Optimized anti-angiogenic therapy may relieve hypoxia and improve drug delivery, which would improve the anti-tumor immune response. In addition, we focus on the potential benefits of a combined approach using immune therapy and treatments designed for vascular normalization. This review emphasizes the potential for a new paradigm of immunotherapy aimed at modulating the tumor microenvironment to change clinical practice. Future research should identify patient populations that may benefit from this approach and quantify the synergistic effects of relevant therapies.
Keywords:
Tumor blood vessel, Tumor microenvironment, Immunotherapy, Gastric cancer
Article Details
How to Cite
KITAHARA, Shuji; SUZUKI, Yasuhiro; EZAKI, Taichi.
How immunotherapy and targeted therapy are changing gastrointestinal cancer treatment.
Medical Research Archives, [S.l.], v. 6, n. 11, nov. 2018.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1870>. Date accessed: 23 nov. 2024.
doi: https://doi.org/10.18103/mra.v6i11.1870.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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38. Kvistborg P, Yewdell JW. Enhancing responses to cancer immunotherapy. Science. Feb 2 2018;359(6375):516-517.
39. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. The Journal of experimental medicine. Oct 2 2000;192(7):1027-1034.
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41. Nikolova M, Lelievre JD, Carriere M, Bensussan A, Levy Y. Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsets. Blood. May 7 2009;113(19):4556-4565.
42. Barber DL, Wherry EJ, Masopust D, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. Feb 9 2006;439(7077):682-687.
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44. Kim ST, Cristescu R, Bass AJ, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nature medicine. Sep 2018;24(9):1449- 1458.
2. Sun Y, Wang R, Qiao M, Xu Y, Guan W, Wang L. Cancer associated fibroblasts tailored tumor microenvironment of therapy resistance in gastrointestinal cancers. Journal of cellular physiology. Sep 2018;233(9):6359- 6369.
3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer journal for clinicians. Jan-Feb 2016;66(1):7-30.
4. Cancer Genome Atlas Research N. Comprehensive molecular charac- terization of gastric adeno- carcinoma. Nature. Sep 11 2014; 513(7517):202-209.
5. Hu B, El Hajj N, Sittler S, Lammert N, Barnes R, Meloni-Ehrig A. Gastric cancer: Classification, histology and application of molecular pathology. Journal of gastrointestinal oncology. Sep 2012;3(3):251-261.
6. Park do J, Thomas NJ, Yoon C, Yoon SS. Vascular endothelial growth factor a inhibition in gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Asso- ciation. Jan 2015;18(1):33-42.
7. Zhang S, Desrosiers J, Aponte-Pieras JR, et al. Human immune responses to H. pylori HLA Class II epitopes identified by immunoinformatic methods. PloS one. 2014;9(4):e94974.
8. Yoshii A, Kitahara S, Ueta H, Matsuno K, Ezaki T. Role of uterine contraction in regeneration of the murine postpartum endometrium. Biology of reproduction. Aug 2014;91(2):32.
9. Kitahara S, Morikawa S, Shimizu K, Abe H, Ezaki T. Alteration of angiogenic patterns on B16BL6 melanoma development promoted in Matrigel. Medical molecular morphology. Mar 2010;43(1):26- 36.
10. Peter Baluk, Shunichi Morikawa, Amy Haskell, Michael Mancuso, McDonald DM. Abnormalities of Basement Membrane on Blood Vessels and Endothelial Sprouts in Tumors. 2003.
11. Jain RK. Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy. Science. 2005;307(5706):58-62.
12. Jain RK. Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. Jun 10 2013;31(17):2205-2218.
13. Martin JD, Fukumura D, Duda DG, Boucher Y, Jain RK. Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity. Cold Spring Harbor perspectives in medicine. Dec 1 2016;6(12).
14. Huang Y, Stylianopoulos T, Duda DG, Fukumura D, Jain RK. Benefits of vascular normalization are dose and time dependent--letter. Cancer research. Dec 1 2013;73 (23):7144-7146.
15. Chen Y, Ramjiawan RR, Reiberger T, et al. CXCR4 inhibition in tumor microenvironment facilitates anti-programmed death receptor-1 immunotherapy in sorafenib-treated hepatocellular carcinoma in mice. Hepatology. May 2015;61(5):1591- 1602.
16. Tian L, Goldstein A, Wang H, et al. Mutual regulation of tumour vessel normalization and immunostimul- atory reprogramming. Nature. Apr 13 2017;544(7649): 250-254.
17. Setia N, Agoston AT, Han HS, et al. A protein and mRNA expression-based classification of gastric cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. Jul 2016;29(7):772- 784.
18. Kitahara S, Suzuki Y, Morishima M, et al. Vasohibin-2 modulates tumor onset in the gastrointestinal tract by normalizing tumor angiogenesis. Molecular cancer. 2014;13:99.
19. Chen Y, Huang Y, Reiberger T, et al. Differential effects of sorafenib on liver versus tumor fibrosis mediated by stromal-derived factor 1 alpha/C-X-C receptor type 4 axis and myeloid differentiation antigen-positive myeloid cell infiltration in mice. Hepatology. Apr 2014;59(4):1435-1447.
20. Chen Y, Ramjiawan RR, Reiberger T, et al. CXCR4 inhibition in tumor microenvironment facilitates anti-PD-1 immunotherapy in sorafenib-treated HCC in mice. Hepatology. Dec 20 2014.
21. Hoos A, Britten C. The immuno-oncology framework: Enabling a new era of cancer therapy. Oncoimmunology. May 1 2012;1(3):334-339.
22. Xu C, Fillmore CM, Koyama S, et al. Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer cell. May 12 2014;25(5):590-604.
23. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. The New England journal of medicine. Aug 19 2010;363(8):711-723.
24. Suzuki Y, Kitahara S, Suematsu T, Oshima M, Sato Y. Requisite role of vasohibin-2 in spontaneous gastric cancer formation and accumulation of cancer-associated fibroblasts. Cancer science. Dec 2017;108(12): 2342-2351.
25. Oh JK, Weiderpass E. Infection and Cancer: Global Distribution and Burden of Diseases. Annals of global health. September - October 2014;80(5):384-392.
26. Lin SJ, Gagnon-Bartsch JA, Tan IB, et al. Signatures of tumour immunity distinguish Asian and non-Asian gastric adenocarcinomas. Gut. Nov 10 2014.
27. Aloisi F, Pujol-Borrell R. Lymphoid neogenesis in chronic inflammatory diseases. Nature reviews. Immuno- logy. Mar 2006;6(3):205- 217.
28. Pelaseyed T, Bergstrom JH, Gustafsson JK, et al. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunological reviews. Jul 2014; 260(1):8-20.
29. Yoon H, Kim N. Diagnosis and management of high risk group for gastric cancer. Gut and liver. Jan 15 2015;9(1):5-17.
30. Putoczki TL, Thiem S, Loving A, et al. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer cell. Aug 12 2013;24(2): 257-271.
31. Hoechst B, Voigtlaender T, Ormandy L, et al. Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology. Sep 2009;50(3):799-807.
32. Gabitass RF, Annels NE, Stocken DD, Pandha HA, Middleton GW. Elevated myeloid-derived suppress- or cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer immunology, immunotherapy : CII. Oct 2011;60 (10):1419-1430.
33. Okazaki T, Chikuma S, Iwai Y, Fagarasan S, Honjo T. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nature immunology. Dec 2013;14(12):1212-1218.
34. Zou Y, Meng J, Chen W, et al. Modulation of phenotypic and functional maturation of murine dendritic cells (DCs) by purified Achyranthes bidentata polysaccha- ride (ABP). International immuno- pharmacology. Aug 2011;11(8): 1103-1108.
35. Osada T, Chong G, Tansik R, et al. The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients. Cancer immunology, immuno- therapy: CII. Aug 2008;57(8): 1115-1124.
36. Gabrilovich DI, Ishida T, Nadaf S, Ohm JE, Carbone DP. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clinical cancer research : an official journal of the American Association for Cancer Research. Oct 1999;5(10):2963-2970.
37. Huang Y, Yuan J, Righi E, et al. Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy. Proceedings of the National Academy of Sciences of the United States of America. Oct 23 2012;109(43):17561-17566.
38. Kvistborg P, Yewdell JW. Enhancing responses to cancer immunotherapy. Science. Feb 2 2018;359(6375):516-517.
39. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. The Journal of experimental medicine. Oct 2 2000;192(7):1027-1034.
40. Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. The Journal of experimental medicine. Dec 21 2009;206(13): 3015-3029.
41. Nikolova M, Lelievre JD, Carriere M, Bensussan A, Levy Y. Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsets. Blood. May 7 2009;113(19):4556-4565.
42. Barber DL, Wherry EJ, Masopust D, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. Feb 9 2006;439(7077):682-687.
43. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proceedings of the National Academy of Sciences of the United States of America. Sep 17 2002;99(19):12293-12297.
44. Kim ST, Cristescu R, Bass AJ, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nature medicine. Sep 2018;24(9):1449- 1458.