ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 29 of 68
Up
УЖМБС 2021, 6(5): 204–213
https://doi.org/10.26693/jmbs06.05.204
Clinical Medicine

Impacts of Inflammatory Microenvironment on the Development of Cancer Relapse after Combined Treatment

Movchan O. V.1, Bagmut I. Yu. 2
Abstract

The purpose of the work was to study the impact of certain elements of the inflammatory microenvironment of the tumor on the development of cancer relapse of main localizations with the amplification of ERBB2 after combined treatment. Materials and methods. 80 patients, who had been treated for the period from 2016 to 2021 in National Cancer Institute, Kyiv, Ukraine. They were 42-78 (average 60) years old, ECOG 0-2, female. All patients histologically proved adenocarcinoma GIII-GIV. Everyone was studied for the level of chitinase-like proteins, cryoglobulins, tumor-associated macrophages in the preoperative (with the first identified disease for the first time, prior to the beginning of the neoadjuvant chemotherapy) and in the postoperative period. 1st block: with a confirmed mutation of HER-2/neu gene (amplification ERBB2 (3+)): a) inflammatory breast cancer (primary-edema form) – 10 people, b) diffuse-infiltrative stomach cancer – 10 people; c) diffuse-infiltrative esophagus cancer – 10 people; d) diffuse-infiltrative colorectal cancer – 10 people. 2nd block: without a confirmed mutation of HER-2/neu gene: a) inflammatory breast cancer (primary edema form) – 10 people; b) a diffuse-infiltrative stomach cancer – 10 people; c) diffuse-infiltrative esophageal cancer – 10 people; d) diffuse-infiltrative colorectal cancer – 10 people. Results and discussion. In patients with infiltrative breast cancer, diffuse-infiltrative stomach cancer, and diffuse-infiltrative esophagus cancer, and diffuse-infiltrative colorectal cancer there was a tendency to an increase in the expression of YKL-39 with the ERBB2 amplification during inflammatory tumor infiltration in the stroma. High expression of Stabilin-1 (2.1±0.70, n = 22) was found compared to patient tumors that did not reveal the amplification of ERBB2 (1.46±0.67, n = 13, p = 0.015). In most patients with amplification ERBB2, the cryoglobulin content was average (298.6±2.5 mg/l; 1.3±0.08%) – 20 (50%), which corresponds to cryoglobulinemia type II; with conditioned cryoglobulinemia (79.4±1.01 mg/l) in 10 (25%); high content (477.3±48 mg/l; 3.4±0.2%) was recorded in 10 (25%), which indicates the type III of cryoglobulinemia [the hazard ratio (HR) = 0.71, 95%, сonfidence interval (CI): 0.22-0.83, p = 0.005] Conclusion. Amplification of ERBB2 and macrophages surroundings markers CD68, M2 subpopulation RS1 (Stabilin-1), chitinase-like proteins YKL-39 and SI-CLP independently identified subgroups of patients with inflammatory breast cancer, diffuse stomach and diffuse esophageal, diffuse colorectal cancer with a bad forecast. In patients with the presence of the amplification of ERBB2 in the inflammatory tumor infiltrate, in the stroma, the higher expression of the chitinase-like protein YKL-39 and M2-polarization RS1 of the marker Stabilin-1, was detected compared to the patient's tumors without amplifying ERBB2. This study shows an important role of quantitative values associated with the tumor phenotype and macrophages in tumor progression, depending on the presence of ERBB2 gain. In patients with cryoglobulinemia with inflammatory cancer the secondary immunodeficiency is developed. This is determined by anomalies in the cell and humoral immune system, and leads to the development of postoperative inflammatory complications and relapses

Keywords: cancer, breast, stomach, esophagus, colorectal, relapse

Full text: PDF (Ua) 350K

References
  1. American Cancer Society. Cancer Treatment & SurvivorshipFacts & Figures 2019-2021. Atlanta: American Cancer Society; 2021. Available from: https://www.cancer.org›cancer-facts-and-statistics
  2. Bednarz-Misa I, Fortuna P, Diakowska D, Jamrozik N, Krzystek-Korpacka M. Distinct Local and Systemic Molecular Signatures in the Esophageal and Gastric Cancers: Possible Therapy Targets and Biomarkers for Gastric Cancer. Int J Mol Sci. 2020; 21: 4509. https://www.ncbi.nlm.nih.gov/pubmed/32630408. https://www.ncbi.nlm.nih.gov/pmc/articles/7349922. https://doi.org/10.3390/ijms21124509
  3. Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer. 2004; 4: 437-447. https://www.ncbi.nlm.nih.gov/pubmed/15170446. https://doi.org/10.1038/nrc1367
  4. Bhangu A, Ali SM, Darzi A, Brown G, Tekkis P. Meta-analysis of survival based on resection margin status following surgery for recurrent rectal cancer. Colorectal Dis. 2012; 14: 1457-1466. https://www.ncbi.nlm.nih.gov/pubmed/22356246. https://doi.org/10.1111/j.1463-1318.2012.03005.x
  5. Chen L, Shi Y, Zhu X, Guo W, Zhang M, Che Y, et al. IL 10 secreted by cancer associated macrophages regulates proliferation and invasion in gastric cancer cells via c Met/STAT3 signaling. Oncol Rep. 2019 Aug; 42(2): 595-604. https://www.ncbi.nlm.nih.gov/pubmed/31233202. https://www.ncbi.nlm.nih.gov/pmc/articles/6610037. https://doi.org/10.3892/or.2019.7206
  6. Cole SW. Chronic inflammation and breast cancer relapse. J Clin Oncol. 2009; 27: 3418-3419. https://www.ncbi.nlm.nih.gov/pubmed/19470918. https://www.ncbi.nlm.nih.gov/pmc/articles/4828958. https://doi.org/10.1200/JCO.2009.21.9782
  7. Sun Y. Tumor microenvironment and cancer therapy resistance. Cancer Lett. 2016; 3(8): 205-215. https://www.ncbi.nlm.nih.gov/pubmed/26272180. https://doi.org/10.1016/j.canlet.2015.07.044
  8. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420: 860-867. HTTPS://WWW.NCBI.NLM.NIH.GOV/PUBMED/12490959. HTTPS://WWW.NCBI.NLM.NIH.GOV/PMC/ARTICLES/2803035. https://doi.org/10.1038/nature01322
  9. Cunningham D, Okines AF, Ashley S. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2010; 362: 858-859. https://www.ncbi.nlm.nih.gov/pubmed/20200397. https://doi.org/10.1056/NEJMc0911925
  10. Li J, Xie Y, Wang X, Li F, Li S, Li M, et al. Prognostic impact of tumor-associated macrophage infiltration in esophageal cancer: a meta-analysis. Future Oncol. 2019; 15: 2303-17. https://www.ncbi.nlm.nih.gov/pubmed/31237146. https://doi.org/10.2217/fon-2018-0669
  11. Wang H, Shao Q, Sun J, et al. Interactions between colon cancer cells and tumor-infiltrated macrophages depending on cancer cell-derived colony stimulating factor 1. Oncoimmunology. 2016; 5(4): e1122157. https://www.ncbi.nlm.nih.gov/pubmed/27141406. https://www.ncbi.nlm.nih.gov/pmc/articles/4839327. https://doi.org/10.1080/2162402X.2015.1122157
  12. Manfredi S, Bouvier AM, Lepage C, Hatem C, Dancourt V, Faivre J. Incidence and patterns of recurrence after resection for cure of colonic cancer in a well defined population. British J Surg. 2006; 9(93): 1115-1122. https://www.ncbi.nlm.nih.gov/pubmed/16804870. https://doi.org/10.1002/bjs.5349
  13. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008; 454: 436-444. https://www.ncbi.nlm.nih.gov/pubmed/18650914. https://doi.org/10.1038/nature07205
  14. Mantovani A, Marchesi F, Porta C, Sica A, Allavena P. Inflammation and cancer: Breast cancer as a prototype. Breast. 2007; 16: S27-S33. https://www.ncbi.nlm.nih.gov/pubmed/17764938. https://doi.org/10.1016/j.breast.2007.07.013
  15. Abbas Z, Rehman S. An Overview of Cancer Treatment Modalities. In: Shahzad HN, Ed. Neoplasm. IntechOpen; 2018. https://doi.org/10.5772/intechopen.76558. Available from: https://www.intechopen.com/books/neoplasm/an-overview-of-cancer-treatment-modalities
  16. McKinley ET, Sui Y, Al-Kofahi Y, Millis BA, Tyska MJ, Roland JT, et al. Optimized multiplex immunofluorescence single-cell analysis reveals tuft cell heterogeneity. JCI Insight. 2017 Jun 2; 2(11): e93487. https://www.ncbi.nlm.nih.gov/pubmed/28570279. https://www.ncbi.nlm.nih.gov/pmc/articles/5453701. https://doi.org/10.1172/jci.insight.93487
  17. McIntosh A, Freedman G, Eisenberg D, Anderson P. Relapse rates and analysis of close or positive margins in patients treated without re-excision before radiation for breast cancer. Am J Clin Oncol. 2007; 30: 146-151. https://www.ncbi.nlm.nih.gov/pubmed/17414463. https://doi.org/10.1097/01.coc.0000251357.45879.7f
  18. Rodríguez-Camacho E, Pita-Fernández S, Pértega-Díaz S, López-Calviño B, Seoane-Pillado T. Characteristics and pattern of recurrence after curative surgery in oesophageal cancer. Rev Esp Enferm Dig. 2015 Sep; 107(9): 539-46. https://www.ncbi.nlm.nih.gov/pubmed/26334460. https://doi.org/10.17235/reed.2015.3748/2015
  19. Miyata H, Yamasaki M, Kurokawa Y, Takiguchi S, Nakajima K, Fujiwara Y. Survival factors in patients with recurrence after curative resection of esophageal carcinomas. Ann Surg Oncol. 2011; 18: 3353-61. https://www.ncbi.nlm.nih.gov/pubmed/21537861. https://doi.org/10.1245/s10434-011-1747-7
  20. Maoz M, Devir M, Inbar M, Inbar-Daniel Z, Sherill-Rofe D, Bloch I, et al. Clinical Implications of Sub-grouping HER2 Positive Tumors by Amplicon Structure and Co-amplified Genes. Sci Rep. 2019 Dec 11; 9(1): 18795. https://www.ncbi.nlm.nih.gov/pubmed/32109238. https://www.ncbi.nlm.nih.gov/pmc/articles/7046641. https://doi.org/10.1038/s41598-020-60492-7
  21. Hao NB, Lü MH, Fan YH, Cao YL, Zhang ZR, Yang SM. Macrophages in Tumor Microenvironments and the Progression of Tumors. Clin Dev Immunol. 2012; 2012: 948098. https://www.ncbi.nlm.nih.gov/pubmed/22778768. https://www.ncbi.nlm.nih.gov/pmc/articles/3385963. https://doi.org/10.1155/2012/948098
  22. Oppenheim J, Fujiwara H. The role of cytokines in cancer Cytokine Growth Factor Rev. 1996; 7(3): 279-288. https://www.ncbi.nlm.nih.gov/pubmed/8971483. https://doi.org/10.1016/s1359-6101(96)00025-1
  23. Cupp MA, Cariolou M, Tzoulaki I, Aune D, Evangelou E, Berlanga-Taylor AJ. Neutrophil to lymphocyte ratio and cancer prognosis: An umbrella review of systematic reviews and meta-analyses of observational studies. BMC Med. 2020; 18: 360. https://www.ncbi.nlm.nih.gov/pubmed/33213430. https://www.ncbi.nlm.nih.gov/pmc/articles/7678319. https://doi.org/10.1186/s12916-020-01817-1
  24. Candido J, Hagemann T. Cancer-related inflammation. J Clin Immunol. 2013 Jan; 33 Suppl 1: S79-84. https://www.ncbi.nlm.nih.gov/pubmed/23225204. https://doi.org/10.1007/s10875-012-9847-0
  25. Méndez-García L , Nava-Castro K , Ochoa-Mercado T, Palacios-Arreola M, Ruiz-Manzano R, Segovia-Mendoza M, et al. Metastasis: Are Cytokines Important Players During Its Development and Progression? J Interferon Cytokine Res. 2019 Jan; 39(1): 39-55. https://www.ncbi.nlm.nih.gov/pubmed/30321090. https://doi.org/10.1089/jir.2018.0024
  26. Roccatello D, Saadoun D, Ramos-Casals M, Tzioufas AG, Fervenza FC, Cacoub P, et al. Cryoglobulinaemia. Nat Rev Dis Primers. 2018; 4(1): 11. https://www.ncbi.nlm.nih.gov/pubmed/30072738. https://doi.org/10.1038/s41572-018-0009-4
  27. Weiguo H. The Role of the Tumor Microenvironment in Waldenström Macroglobulinemia. Doctoral Dissertations. 2019. Fvailable from: https://scholars.unh.edu/dissertation/2447
  28. Vrána D, Matzenauer M, Neoral Č, Aujeský R, Vrba R, Melichar B, et al. From Tumor Immunology to Immunotherapy in Gastric and esophagus Cancer. Int J Mol Sci. 2019; 20: 13. https://www.ncbi.nlm.nih.gov/pubmed/30577521. https://www.ncbi.nlm.nih.gov/pmc/articles/6337592. https://doi.org/10.3390/ijms20010013
  29. Qu X, Tang Y, Hua S. Immunological Approaches Towards Cancer and Inflammation: A Cross Talk. Front Immunol. 2018 Mar 20; 9: 563. https://www.ncbi.nlm.nih.gov/pubmed/29662489. https://www.ncbi.nlm.nih.gov/pmc/articles/5890100. https://doi.org/10.3389/fimmu.2018.00563
  30. Van Maaren MC, Strobbe LJA, Smidt ML, Moossdorff M, Poortmans PMP, Siesling S. Ten-year conditional recurrence risks and overall and relative survival for breast cancer patients in the Netherlands: taking account of event-free years. Eur J Cancer. 2018; 102: 82-94. https://www.ncbi.nlm.nih.gov/pubmed/30144661. https://doi.org/10.1016/j.ejca.2018.07.124
  31. Land WG. The Role of Damage-Associated Molecular Patterns (DAMPs) in Human Diseases: Part II: DAMPs as diagnostics, prognostics and therapeutics in clinical medicine. Sultan Qaboos Univ Med J. 2015; 15: e157-e170.
  32. Oshi M, Newman S, Tokumaru Y, Yan L, Matsuyama R, Endo I, et al. Intra-Tumoral Angiogenesis Is Associated with Inflammation, Immune Reaction and Metastatic Relapse in Breast Cancer. Int J Mol Sci. 2020; 21: 6708. https://www.ncbi.nlm.nih.gov/pubmed/32933189. https://www.ncbi.nlm.nih.gov/pmc/articles/7555442. https://doi.org/10.3390/ijms21186708
  33. Voss RK, Lin JC, Roper MT, Al-Temimi MH, Ruan JH, Tseng WH, et al. Adjuvant Chemotherapy Does Not Improve Recurrence-Free Survival in Patients With Stage 2 or Stage 3 Rectal Cancer After Neoadjuvant Chemoradiotherapy and Total Mesorectal Excision. Dis Colon Rectum. 2020 Apr; 63(4): 427-440. https://www.ncbi.nlm.nih.gov/pubmed/31996583.
  34. https://doi.org/10.1097/DCR.0000000000001558
  35. Reuben J, Bang-Ning L. Immunology of Inflammatory Breast Cancer. Research Gate. In: Inflammatory Breast Cancer. 2012 Mar. p.207-224. https://doi.org/10.1007/978-94-007-3907-9_17
  36. Pellegrino B, Hlavata Z, Migali C, De Silva P, Aiello M, Willard-Gallo K, et al. Luminal Breast Cancer: Risk of Recurrence and Tumor-Associated Immune Suppression. Mol Diagn Ther. 2021 Jul; 25(4) :409-424. https://www.ncbi.nlm.nih.gov/pubmed/33974235. https://www.ncbi.nlm.nih.gov/pmc/articles/8249273. https://doi.org/10.1007/s40291-021-00525-7
  37. Sulciner ML, Serhan CN, Gilligan MM, Mudge DK, Chang J, Gartung A, et al. Resolvins suppress tumor growth and enhance cancer therapy. J Exp Med. 2018; 215: 115-140. https://www.ncbi.nlm.nih.gov/pubmed/29191914. https://www.ncbi.nlm.nih.gov/pmc/articles/5748851. https://doi.org/10.1084/jem.20170681
  38. Tomulescu V, Stanescu C, Blajut C, Barbulescu L, Droc G, Herlea V, et al. Robotic Approach in Benign and Malignant Esophageal Tumors; A Preliminary Seven Case Series. Chirurgia. 2018; 113: 202-209. https://www.ncbi.nlm.nih.gov/pubmed/29733012. https://doi.org/10.21614/chirurgia.113.2.202
  39. Ferri LE, Law S, Wong KH, Kwok KF, Wong J. The influence of technical complications on postoperative outcome and survival after esophagectomy. Ann Surg Oncol. 2006; 13: 557-564. https://www.ncbi.nlm.nih.gov/pubmed/16485146. https://doi.org/10.1245/ASO.2006.04.040
  40. Esmatabadi MJ, Bakhshinejad B, Motlagh FM, Babashah S, Sadeghizadeh M. Therapeutic resistance and cancer relapse mechanisms: Unfolding the story of tumour coming back. J Biosci. 2016; 41: 497-506. https://www.ncbi.nlm.nih.gov/pubmed/27581940. https://doi.org/10.1007/s12038-016-9624-y
  41. Yagi T, Baba Y, Okadome K, Kiyozumi Y, Hiyoshi Y, Ishimoto T, et al. Tumour-associated macrophages are associated with poor prognosis and programmed death ligand 1 expression in esophageal cancer. Eur J Cancer. 2019; 111: 38-49. https://www.ncbi.nlm.nih.gov/pubmed/30822683. https://doi.org/10.1016/j.ejca.2019.01.018
  42. Miyamoto R, Inagawa S, Sano N, Tadano S, Adachi S, Yamamoto M. The hypercryoglobulinemia predicts short-term and long-term outcomes in gastric cancer patients. Eur J Surg Oncol. 2018; 44: 607-612. https://www.ncbi.nlm.nih.gov/pubmed/29478743. https://doi.org/10.1016/j.ejso.2018.02.003
  43. Huang, L, Liu, S, Lei, Y, Wang, K, Xu, M, Chen, Y, et al. Systemic immune-inflammation index, thymidine phosphorylase and survival of localized gastric cancer patients after curative resection. Oncotarget. 2016; 7: 44185-44193. https://www.ncbi.nlm.nih.gov/pubmed/27283904. https://www.ncbi.nlm.nih.gov/pmc/articles/5190088. https://doi.org/10.18632/oncotarget.9923
  44. Kim TS, da Silva E, Coit DG, Tang LH. Intratumoral Immune Response to Gastric Cancer Varies by Molecular and Histologic Subtype. Am J Surg Pathol. 2019 Jun 4; 3(6): 871-860. https://www.ncbi.nlm.nih.gov/pubmed/30969179. https://www.ncbi.nlm.nih.gov/pmc/articles/6867704. https://doi.org/10.1097/PAS.0000000000001253
  45. Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014; 15: 1389-1396. https://doi.org/10.1016/S1470-2045(14)70473-5
  46. Ishiguro S, Akasu T, Fujita S, Yamamoto S, Kusters M, Moriya Y. Pelvic exenteration for clinical T4 rectal cancer: Oncologic outcome in 93 patients at a single institution over a 30-year period. Surgery. 2009; 145: 189-195. https://www.ncbi.nlm.nih.gov/pubmed/19167974. https://doi.org/10.1016/j.surg.2008.09.014
  47. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, et al. Drug resistance in cancer: An overview. Cancers. 2014; 6: 1769-1792. https://www.ncbi.nlm.nih.gov/pubmed/25198391. https://www.ncbi.nlm.nih.gov/pmc/articles/4190567. https://doi.org/10.3390/cancers6031769
  48. Heald RJ, Ryall RD. Relapse and survival after total mesorectal excision for rectal cancer. Lancet. 1986; 1: 1479-1482. https://doi.org/10.1016/S0140-6736(86)91510-2
  49. Tuomisto AE, Mäkinen MJ, Väyrynen JP. Systemic inflammation in colorectal cancer: Underlying factors, effects, and prognostic significance. World J Gastroenterol. 2019; 25(31): 4383-4404. https://www.ncbi.nlm.nih.gov/pubmed/31496619. https://www.ncbi.nlm.nih.gov/pmc/articles/6710177. https://doi.org/10.3748/wjg.v25.i31.4383
  50. Varkaris A, Katsiampoura A, Davis JS, Shah N, Lam M, Frias RL, et al. Circulating inflammation signature predicts overall survival and relapse-free survival in metastatic colorectal cancer. Br J Cancer. 2019; 120: 340-345. https://www.ncbi.nlm.nih.gov/pubmed/30636774. https://www.ncbi.nlm.nih.gov/pmc/articles/6353894. https://doi.org/10.1038/s41416-018-0360-y
  51. Moriya Y, Akasu T, Fujita S, Yamamoto S. Total pelvic exenteration with distal sacrectomy for fixed recurrent rectal cancer in the pelvis. Dis. Colon Rectum. 2004; 47: 2047-2053. https://www.ncbi.nlm.nih.gov/pubmed/15657653. https://doi.org/10.1007/s10350-004-0714-9
  52. Mirnezami, A, Mirnezami, R, Chandrakumaran, K, Sasapu, K, Sagar, P, Finan, P. Increased local relapse and reduced survival from colorectal cancer following anastomotic leak: Systematic review and meta-analysis. Ann Surg. 2011; 253: 890-899. https://www.ncbi.nlm.nih.gov/pubmed/21394013. https://doi.org/10.1097/SLA.0b013e3182128929
  53. Larionova I, Tuguzbaeva G, Ponomaryova A, Stakheyeva M, Cherdyntseva N. Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate. Cancers Frontiers Oncology. 2020; 10: 2232. https://www.ncbi.nlm.nih.gov/pubmed/33194645. https://www.ncbi.nlm.nih.gov/pmc/articles/7642726. https://doi.org/10.3389/fonc.2020.566511
  54. Kzhyshkowska J, Larionova I, Liu T. YKL-39 as a Potential New Target for Anti-Angiogenic Therapy in Cancer. Front Immunol. 2020; 10: 2930. https://www.ncbi.nlm.nih.gov/pubmed/32038607. https://www.ncbi.nlm.nih.gov/pmc/articles/6988383. https://doi.org/10.3389/fimmu.2019.02930