Analysis of systemic immunity and inflammation in the prognosis of gastric adenocarcinoma

Objective: to study the state of cellular immunity in patients with gastric adenocarcinoma.

Materials and methods. From 2017 to 2018, 45 previously untreated patients with gastric adenocarcinoma (25 with stage I–III, 20 with stage IV) received surgical / combined treatment or independent chemotherapy, respectively, at the N. N. Blokhin National Medical Research

Center of Oncology. Peripheral blood sampling was carried out before starting treatment. We studied the cellular composition of peripheral blood, as well as systemic immunity parameters determined by flow cytometry (CD3⁺CD4⁺; CD3⁺CD8⁺; CD4⁺CD8⁺; CD4⁺/CD8⁺; CD3^–CD16⁺CD56⁺; CD3^–CD19⁺), and their prognostic significance in relation to overall survival and progression-free survival.

Results. The prognostic value of the relative indicator of platelet lymphocytic index was determined: progression-free survival in patients with a high level of platelet-lymphocytic index (>208.7) was higher: 8.1 months versus 4.5 months (p = 0.0027). A favorable prognosis for overall survival was an increase in the number of CD3^–CD19⁺ lymphocytes (hazard ratio (HR) 0.91; 95 % confidence interval (CI) 0.85–0.97; p = 0.007), and an unfavorable prognosis was an increase in the number of neutrophils (HR 1.26; 95 % CI 1.05–1.50; p = 0.012), platelet count (HR 1.01; 95 % CI 1.0–1.01; p = 0.043), as well as an increase in the number of NK cells (HR 1.04, 95 % CI 1.0–1.09; p = 0.029).

Conclusion. Indicators of the cellular composition of peripheral blood, characterizing a systemic inflammatory reaction, as well as indicators of systemic immunity, can serve as additional prognostic factors for gastric cancer.

1. Global Burden of Disease Cancer Collaboration, Fitzmaurice C., Allen C. et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the Global Burden of Disease Study. JAMA Oncol 2017;3(4):524–48. DOI: 10.1001/jamaoncol.2016.5688.

2. Davydov M.I., Aksel’ E.M. The incidence of malignant neoplasms of the population of Russia and the CIS countries in 2004. Vestnik RONTs im. N.N. Blokhina RAMN = Bulletin of the Russian Research Center N.N. Blokhin RAMS 2008; 19(2 att. 1):52–90. (In Russ.).

3. Davydov M.I., Ter-Ovanesov M.D. A modern strategy for the surgical treatment of gastric cancer. Sovremennaya onkologiya = Modern Oncology 2000;2(1):4–10. (In Russ.).

4. Yazici O., Sendur M.A., Ozdemir N., Aksoy S. Targeted therapies in gastric cancer and future perspectives. World J Gastroenterol 2016;22(2):471–89. DOI: 10.3748/wjg.v22.i2.471.

5. Waddell T., Verheij M., Allum W. et al. Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24 Suppl 6:vi57–63. DOI: 10.1093/annonc/mdt344.

6. Okines A.F., Norman A.R., McCloud P. et al. Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabinebased combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol 2009;20(9):1529–34. DOI: 10.1093/annonc/mdp047.

7. Berezhnaya N.M. The interaction of cells of the immune system with other components of the microenvironment. Onkologiya = Oncology 2009;1(2):86–93. (In Russ.).

8. Coussens L.M., Werb Z. Inflammation and cancer. Nature 2002;420(6917):860–7. DOI: 10.1038/nature01322.

9. Takenaka Y., Oya R., Kitamiura T. et al. Platelet count and platelet-lymphocyte ratio as prognostic markers for head and neck squamous cell carcinoma: Meta- analysis. Head Neck 2018;40(12): 2714–23. DOI: 10.1002/hed.25366.

10. Mori M., Shuto K., Kosugi C. et al. An increase in the neutrophil-tolymphocyte ratio during adjuvant chemotherapy indicates a poor prognosis in patients with stage II or III gastric cancer. BMC Cancer 2018;18(1):1261. DOI: 10.1186/s12885-018-5171-2.

11. Galon J., Pages F., Marincola F.M. et al. Cancer classification using the immunoscore: a worldwide task force. J Transl Med 2012;10:205. DOI: 10.1186/1479-5876-10-205.

12. Passardi A., Scarpi E., Cavanna L. et al. Inflammatory indexes as predictors of prognosis and bevacizumab efficacy in patients with metastatic colorectal cancer. Oncotarget 2016;7(22):33210–9. DOI: 10.18632/oncotarget.8901.

13. Gunaldi M., Goksu S., Erdem D. et al. Prognostic impact of platelet/lymphocyte and neutrophil/lymphocyte ratios in patients with gastric cancer: a multicenter study. Int J Clin Exp Med 2015;8(4):5937–42.

14. Kutukova S.I., Belyak N.P., Raskin G.A. et al. Cistemnoe vospalenie i immunologicheskoe mikrookruzhenie v prognoze techeniya solidnykh opukholey. Zlokachestvennye opukholi = Malignant Tumors 2019;9(1):29–37. (In Russ.). DOI: 10.18027/2224-5057-2019-9-1-29-37.

15. Desbois M., Rusakiewicz S., Locher C. et al. Natural killer cells in non-hemato-poietic malignancies. Front Immunol 2012;3:395. DOI: 10.3389/fimmu.2012.00395.

16. Liu G.O., Song-Wen H., Ke P. Prognostic significance of preoperative CD8+ central memory T cells for operable and advanced gastric cancer Int J Clin Exp Pathol 2017;10(3):3424–30.

17. Mantovani A., Romero P., Palucka A.K., Marincola F.M. Tumor immunity: effector response to tumor and role of the microenvironment. Lanset 2008;371(9614): 771–83. DOI: 10.1016/S0140-6736(08)60241-X.

18. Tupicin N.N. Immunophenotype of breast cancer. Mammary Cancer. Eds.: N.E. Kushlinskii, S.M. Portnoy, K.G. Laktionov. Мoscow: RAMN, 2005. Pp. 174–197. (In Russ.).