Stromal Protein-Mediated Immune Regulation in Digestive Cancers

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Jan 20

PMID 33466303

Citations 13

Authors

Pia Gamradt

Christelle De La Fouchardiere

Ana Hennino

Affiliations

Soon will be listed here.

Abstract

The stromal tumor microenvironment (TME) consists of immune cells, vascular and neural structures, cancer-associated fibroblasts (CAFs), as well as extracellular matrix (ECM), and favors immune escape mechanisms promoting the initiation and progression of digestive cancers. Numerous ECM proteins released by stromal and tumor cells are crucial in providing physical rigidity to the TME, though they are also key regulators of the immune response against cancer cells by interacting directly with immune cells or engaging with immune regulatory molecules. Here, we discuss current knowledge of stromal proteins in digestive cancers including pancreatic cancer, colorectal cancer, and gastric cancer, focusing on their functions in inhibiting tumor immunity and enabling drug resistance. Moreover, we will discuss the implication of stromal proteins as therapeutic targets to unleash efficient immunotherapy-based treatments.

Citing Articles

Role and value of the tumor microenvironment in the progression and treatment resistance of gastric cancer (Review).

Yun H, Dong F, Wei X, Yan X, Zhang R, Zhang X Oncol Rep. 2024; 53(1).

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Stiffness-induced cancer-associated fibroblasts are responsible for immunosuppression in a platelet-derived growth factor ligand-dependent manner.

Gamradt P, Thierry K, Masmoudi M, Wu Z, Hernandez-Vargas H, Bachy S PNAS Nexus. 2023; 2(12):pgad405.

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References

Hamidi H, Pietila M, Ivaska J . The complexity of integrins in cancer and new scopes for therapeutic targeting. Br J Cancer. 2016; 115(9):1017-1023. PMC: 5117799. DOI: 10.1038/bjc.2016.312. View

Kudo A . Introductory review: periostin-gene and protein structure. Cell Mol Life Sci. 2017; 74(23):4259-4268. PMC: 11107487. DOI: 10.1007/s00018-017-2643-5. View

Ko A, LoConte N, Tempero M, Walker E, Kelley R, Lewis S . A Phase I Study of FOLFIRINOX Plus IPI-926, a Hedgehog Pathway Inhibitor, for Advanced Pancreatic Adenocarcinoma. Pancreas. 2015; 45(3):370-5. PMC: 5908466. DOI: 10.1097/MPA.0000000000000458. View

Whatcott C, Han H, Posner R, Hostetter G, Von Hoff D . Targeting the tumor microenvironment in cancer: why hyaluronidase deserves a second look. Cancer Discov. 2011; 1(4):291-6. PMC: 3204883. DOI: 10.1158/2159-8290.CD-11-0136. View

Jefferies C . Regulating IRFs in IFN Driven Disease. Front Immunol. 2019; 10:325. PMC: 6449421. DOI: 10.3389/fimmu.2019.00325. View

Baaten B, Li C, Bradley L . Multifaceted regulation of T cells by CD44. Commun Integr Biol. 2011; 3(6):508-12. PMC: 3038050. DOI: 10.4161/cib.3.6.13495. View

Caon I, Bartolini B, Parnigoni A, Carava E, Moretto P, Viola M . Revisiting the hallmarks of cancer: The role of hyaluronan. Semin Cancer Biol. 2019; 62:9-19. DOI: 10.1016/j.semcancer.2019.07.007. View

De Jesus-Acosta A, Sugar E, ODwyer P, Ramanathan R, Von Hoff D, Rasheed Z . Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma. Br J Cancer. 2019; 122(4):498-505. PMC: 7029016. DOI: 10.1038/s41416-019-0683-3. View

Schreiber R, Old L, Smyth M . Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011; 331(6024):1565-70. DOI: 10.1126/science.1203486. View

10.

Lin C, Wang C, Chao Y, Lai M, Shan Y . The significance of the co-existence of osteopontin and tumor-associated macrophages in gastric cancer progression. BMC Cancer. 2015; 15:128. PMC: 4384326. DOI: 10.1186/s12885-015-1114-3. View

11.

Tang M, Liu B, Bu X, Zhao P . Cross-talk between ovarian cancer cells and macrophages through periostin promotes macrophage recruitment. Cancer Sci. 2018; 109(5):1309-1318. PMC: 5980394. DOI: 10.1111/cas.13567. View

12.

Kai F, Drain A, Weaver V . The Extracellular Matrix Modulates the Metastatic Journey. Dev Cell. 2019; 49(3):332-346. PMC: 6527347. DOI: 10.1016/j.devcel.2019.03.026. View

13.

Goldman J, Eckhardt S, Borad M, Curtis K, Hidalgo M, Calvo E . Phase I dose-escalation trial of the oral investigational Hedgehog signaling pathway inhibitor TAK-441 in patients with advanced solid tumors. Clin Cancer Res. 2014; 21(5):1002-9. DOI: 10.1158/1078-0432.CCR-14-1234. View

14.

Drev D, Harpain F, Beer A, Stift A, Gruber E, Klimpfinger M . Impact of Fibroblast-Derived SPARC on Invasiveness of Colorectal Cancer Cells. Cancers (Basel). 2019; 11(10). PMC: 6827058. DOI: 10.3390/cancers11101421. View

15.

Ohno S, Tachibana M, Fujii T, Ueda S, Kubota H, Nagasue N . Role of stromal collagen in immunomodulation and prognosis of advanced gastric carcinoma. Int J Cancer. 2002; 97(6):770-4. DOI: 10.1002/ijc.10144. View

16.

Gonzalez-Gonzalez L, Alonso J . Periostin: A Matricellular Protein With Multiple Functions in Cancer Development and Progression. Front Oncol. 2018; 8:225. PMC: 6005831. DOI: 10.3389/fonc.2018.00225. View

17.

Simon T, Bromberg J . Regulation of the Immune System by Laminins. Trends Immunol. 2017; 38(11):858-871. PMC: 5669817. DOI: 10.1016/j.it.2017.06.002. View

18.

Hersh E, ODay S, Ribas A, Samlowski W, Gordon M, Shechter D . A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Cancer. 2009; 116(1):155-63. DOI: 10.1002/cncr.24720. View

19.

Garcia-Garcia A, Martin I . Extracellular Matrices to Modulate the Innate Immune Response and Enhance Bone Healing. Front Immunol. 2019; 10:2256. PMC: 6764079. DOI: 10.3389/fimmu.2019.02256. View

20.

Viloria K, Hill N . Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation. Biomol Concepts. 2016; 7(2):117-32. DOI: 10.1515/bmc-2016-0004. View