AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
PDF (780.5 KB)
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Original Article | Open Access

The prognostic landscape of genes and infiltrating immune cells in cytokine induced killer cell treated-lung squamous cell carcinoma and adenocarcinoma

Jian Wang1Fan Yang2Qian Sun1Ziqing Zeng1Min Liu1Wenwen Yu1Peng Zhang1Jinpu Yu3Lili Yang1Xinwei Zhang2Xiubao Ren1,2Feng Wei1 ( )
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China
Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China
Show Author Information

Abstract

Objective

Patients with non–small cell lung cancer (NSCLC) respond differently to cytokine-induced killer cell (CIK) treatment. Therefore, potential prognostic markers to identify patients who would benefit from CIK treatment must be elucidated. The current research aimed at identifying predictive prognostic markers for efficient CIK treatment of patients with NSCLC.

Methods

Patients histologically diagnosed with NSCLC were enrolled from the Tianjin Medical University Cancer Institute and Hospital. We performed whole-exome sequencing (WES) on the tumor tissues and paired adjacent benign tissues collected from 50 patients with NSCLC, and RNA-seq on tumor tissues of 17 patients with NSCLC before CIK immunotherapy treatment. Multivariate Cox proportional hazard regression analysis was used to analyze the association between clinical parameters and prognostic relevance. WES and RNA-seq data between lung squamous cell carcinoma (SCC) and adenocarcinoma (Aden) were analyzed and compared.

Results

The pathology subtype of lung cancer was the most significantly relevant clinical parameter associated with DFS, as analyzed by multivariate Cox proportional hazard regression (P = 0.031). The patients with lung SCC showed better CIK treatment efficacy and extended DFS after CIK treatment. Relatively low expression of HLA class Ⅱ genes and checkpoint molecules, and less immunosuppressive immune cell infiltration were identified in the patients with lung SCC.

Conclusions

Coordinated suppression of the expression of HLA class Ⅱ genes and checkpoint molecules, as well as less immune suppressive cell infiltration together contributed to the better CIK treatment efficacy in lung SCC than lung Aden.

Electronic Supplementary Material

Download File(s)
cbm-18-4-1134_ESM.pdf (920.9 KB)

References

1

Feng RM, Zong YN, Cao SM, Xu RH. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond). 2019; 39: 22.

2

Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer. 2014; 14: 535–6.

3

Tsao MS, Sakurada A, Cutz JC, Zhu CQ, Kamel-Reid S, Squire J, et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med. 2005; 353: 133–44.

4

Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013; 368: 2385–94.

5

Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004; 304: 1497–500.

6

Gandara DR, Hammerman PS, Sos ML, Lara PN, Jr, Hirsch FR. Squamous cell lung cancer: from tumor genomics to cancer therapeutics. Clin Cancer Res. 2015; 21: 2236–3.

7

Riely GJ, Yu HA. EGFR: the paradigm of an Oncogene-Driven Lung Cancer. Clin Cancer Res. 2015; 21: 2221–6.

8

Anagnostou VK, Brahmer JR. Cancer immunotherapy: a future paradigm shift in the treatment of non–small cell lung cancer. Clin Cancer Res. 2015; 21: 976–4.

9

Chen D, Sha H, Hu T, Dong S, Zhang J, Liu S, et al. Cytokine-induced killer cells as a feasible adoptive immunotherapy for the treatment of lung cancer. Cell Death Disease. 2018; 9: 366.

10

Yang L, Ren B, Li H, Yu J, Cao S, Hao X, et al. Enhanced antitumor effects of DC-activated CIKs to chemotherapy treatment in a single cohort of advanced non-small-cell lung cancer patients. Cancer Immunol Immunother. 2013; 62: 65–73.

11

Hui Z, Zhang X, Ren B, Li R, Ren X. Rapid response of advanced squamous non-small cell lung cancer with thrombocytopenia after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells. Front Immunol. 2015; 6: 633.

12

Li H, Wang C, Yu J, Cao S, Wei F, Zhang W, et al. Dendritic cell-activated cytokine-induced killer cells enhance the anti-tumor effect of chemotherapy on non-small cell lung cancer in patients after surgery. Cytotherapy. 2009; 11: 1076–83.

13

Li M, Wang Y, Wei F, An X, Zhang N, Cao S, et al. Efficiency of cytokine-induced killer cells in combination with Chemotherapy for Triple-Negative Breast Cancer. J Breast Cancer. 2018; 21: 150–7.

14

Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015; 14: 847–56.

15

Hellmann MD, Nathanson T, Rizvi H, Creelan BC, Sanchez-Vega F, Ahuja A, et al. Genomic features of response to combination immunotherapy in patients with advanced non-small-cell lung cancer. Cancer Cell. 2018; 33: 843–52.e844.

16

Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019; 51: 202–6.

17

Charoentong P, Finotello F, Angelova M, Mayer C, Efremova M, Rieder D, et al. Pan-cancer Immunogenomic analyses reveal Genotype-Immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep. 2017; 18: 248–62.

18

Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010; 17: 1471–4.

19

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5: 649–55.

20

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009; 45: 228–47.

21

Zhao H, Wang Y, Yu J, Wei F, Cao S, Zhang X, et al. Autologous cytokine-induced killer cells improves overall survival of metastatic colorectal cancer patients: results from a phase Ⅱ clinical trial. Clin Colorectal Cancer. 2016; 15: 228–35.

22

Liu L, Gao Q, Jiang J, Zhang J, Song X, Cui J, et al. Randomized, multicenter, open-label trial of autologous cytokine-induced killer cell immunotherapy plus chemotherapy for squamous non-small-cell lung cancer: NCT01631357. Signal Transduct Target Ther. 2020; 5: 244.

23

Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25: 1754–60.

24

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The sequence alignment/Map format and SAMtools. Bioinformatics. 2009; 25: 2078–9.

25

DePristo MA, Banks E, Poplin R, Garimella KV, Maguire JR, Hartl C, et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011; 43: 491.

26

Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015; 12: 357.

27

Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15: 550.

28

Yu G, Wang L-G, Han Y, He Q-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16: 284–7.

29

Van den Berge K, Perraudeau F, Soneson C, Love MI, Risso D, Vert JP, et al. Observation weights unlock bulk RNA-seq tools for zero inflation and single-cell applications. Genome Biol. 2018; 19: 24.

30

Aran D, Hu Z, Butte AJ. xCell: digitally portraying the tissue cellular heterogeneity landscape. Genome Biol. 2017; 18: 220.

31

Sechler M, Cizmic AD, Avasarala S, Van Scoyk M, Brzezinski C, Kelley N, et al. Non-small-cell lung cancer: molecular targeted therapy and personalized medicine - drug resistance, mechanisms, and strategies. Pharmgenomics Pers Med. 2013; 6: 25–36.

32

Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell. 2016; 165: 35–44.

33

Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015; 350: 207–11.

34

Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, et al. Molecular determinants of response to anti–programmed cell death (PD)-1 and anti–programmed death-ligand 1 (PD-L1) blockade in patients with non–small-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol. 2018; 36: 633–41.

35

Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci. 2004; 101: 13306–11.

36

Network CGAR. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014; 511: 543–50.

37

Jiao XD, He X, Qin BD, Liu K, Wu Y, Liu J, et al. The prognostic value of tumor mutation burden in EGFR-mutant advanced lung adenocarcinoma, an analysis based on cBioPortal data base. J Thorac Dis. 2019; 11: 4507–15.

38

Offin M, Rizvi H, Tenet M, Ni A, Sanchez-Vega F, Li BT, et al. Tumor mutation burden and efficacy of EGFR-Tyrosine kinase inhibitors in patients with EGFR-Mutant lung cancers. Clin Cancer Res. 2019; 25: 1063–9.

39

Lin C, Shi X, Zhao J, He Q, Fan Y, Xu W, et al. Tumor mutation burden correlates with efficacy of chemotherapy/targeted therapy in advanced non-small cell lung cancer. Front Oncol. 2020; 10: 480.

40

Brower V. Chimeric antigen receptor T-cell immunotherapy tackles blood cancers. J Natl Cancer Inst. 2015; 107: djv112.

41

Turcotte S, Rosenberg SA. Immunotherapy for metastatic solid cancers. Adv Surg. 2011; 45: 341–60.

42

Hontscha C, Borck Y, Zhou H, Messmer D, Schmidt-Wolf IG. Clinical trials on CIK cells: first report of the international registry on CIK cells (IRCC). J Cancer Res Clin Oncol. 2011; 137: 305–10.

43

Schmidt-Wolf IG, Negrin RS, Kiem HP, Blume KG, Weissman IL. Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity. J Exp Med. 1991; 174: 139–49.

44

Ochoa AC, Gromo G, Alter BJ, Sondel PM, Bach FH. Long-term growth of lymphokine-activated killer (LAK) cells: role of anti-CD3, beta-IL 1, interferon-gamma and -beta. J Immunol. 1987; 138: 2728–33.

45

Lu PH, Negrin RS. A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency. J Immunol. 1994; 153: 1687–96.

46

Franceschetti M, Pievani A, Borleri G, Vago L, Fleischhauer K, Golay J, et al. Cytokine-induced killer cells are terminally differentiated activated CD8 cytotoxic T-EMRA lymphocytes. Exp Hematol. 2009; 37: 616–28 e612.

47

Zhu XP, Xu YH, Zhou J, Pan XF. A clinical study evaluating dendritic and cytokine-induced killer cells combined with concurrent radiochemotherapy for stage ⅢB non-small cell lung cancer. Genet Mol Res. 2015; 14: 10228–35.

48

Zhang J, Zhu L, Du H, He X, Yin Y, Gu Y, et al. Autologous cytokine-induced killer cell therapy in lung cancer patients: a retrospective study. Biomed Pharmacother. 2015; 70: 248–52.

49

Li DP, Li W, Feng J, Chen K, Tao M. Adjuvant chemotherapy with sequential cytokine-induced killer (CIK) cells in stage IB non-small cell lung cancer. Oncol Res. 2015; 22: 67–74.

50

Moor K, Diard M, Sellin ME, Felmy B, Wotzka SY, Toska A, et al. High-avidity IgA protects the intestine by enchaining growing bacteria. Nature. 2017; 544: 498–502.

51

Mantis NJ, Rol N, Corthesy B. Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol. 2011; 4: 603–11.

52

Pabst O. New concepts in the generation and functions of IgA. Nat Rev Immunol. 2012; 12: 821–32.

53

Slack E, Balmer ML, Macpherson AJ. B cells as a critical node in the microbiota-host immune system network. Immunol Rev. 2014; 260: 50–66.

54

Yang Z, Tao Y, Xu X, Cai F, Yu Y, Ma L. Bufalin inhibits cell proliferation and migration of hepatocellular carcinoma cells via APOBEC3F induced intestinal immune network for IgA production signaling pathway. Biochem Biophys Res Commun. 2018; 503: 2124–31.

55

Thibodeau J, Bourgeois-Daigneault M-C, Lapointe R. Targeting the MHC Class Ⅱ antigen presentation pathway in cancer immunotherapy. Oncoimmunology. 2012; 1: 908–16.

56

Verneris MR, Karimi M, Baker J, Jayaswal A, Negrin RS. Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells. Blood. 2004; 103: 3065–72.

57

Karimi M, Cao TM, Baker JA, Verneris MR, Soares L, Negrin RS. Silencing human NKG2D, DAP10, and DAP12 reduces cytotoxicity of activated CD8+ T cells and NK cells. J Immunol. 2005; 175: 7819–28.

58

Patel SJ, Sanjana NE, Kishton RJ, Eidizadeh A, Vodnala SK, Cam M, et al. Identification of essential genes for cancer immunotherapy. Nature. 2017; 548: 537.

59

Rodríguez JA. HLA-mediated tumor escape mechanisms that may impair immunotherapy clinical outcomes via T-cell activation. Oncol Lett. 2017; 14: 4415–27.

60

Network CGAR. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012; 489: 519.

61

Campbell JD, Alexandrov A, Kim J, Wala J, Berger AH, Pedamallu CS, et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet. 2016; 48: 607–16.

Cancer Biology & Medicine
Pages 1134-1147
Cite this article:
Wang J, Yang F, Sun Q, et al. The prognostic landscape of genes and infiltrating immune cells in cytokine induced killer cell treated-lung squamous cell carcinoma and adenocarcinoma. Cancer Biology & Medicine, 2021, 18(4): 1134-1147. https://doi.org/10.20892/j.issn.2095-3941.2021.0023

58

Views

0

Downloads

2

Crossref

3

Web of Science

4

Scopus

Altmetrics

Received: 09 January 2021
Accepted: 20 May 2021
Published: 01 November 2021
©2021 Cancer Biology & Medicine.

Creative Commons Attribution-NonCommercial 4.0 International License

Return