Relationship Between Kita-Kyushu Lung Cancer Antigen-1 Expression and Prognosis of Cases with Lung Squamous Cell Carcinoma

Overview

Journal Transl Cancer Res

Specialty Oncology

Date 2022 Feb 4

PMID 35116371

Authors

Yoshinobu Ichiki

Takashi Fukuyama

Haruki Ohmiya

Mari Ueno

Shinya Yanagi

Yoshiro Kanasaki

Hidenori Goto

Shuji Mikami

Hitoshi Yamazaki

Kozo Nakanishi

Tsuyoshi Ishida

Affiliations

Soon will be listed here.

Abstract

Background: Previously, we identified the highly immunogenic cancer testicular antigen named Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1). In this study, we analyzed the effect of KK-LC-1 expression on the prognosis of patients with resected squamous cell lung cancer.

Methods: Fifty squamous cell lung cancer patients, who received complete resection, were enrolled in this study. The expressions of KK-LC-1, CD8, human leukocyte antigen (HLA) class I, and programmed cell death protein ligand-1 (PD-L1) were assessed via immunohistochemistry staining using the specimens obtained from the participants. The association between the expression of the abovementioned molecules and patient prognosis was investigated.

Results: KK-LC-1 expression was observed in 21 of 50 recruited cases (42%). However, no significant correlation was found between KK-LC-1 expression and patient prognosis. The prognosis was significantly better in lung cancer cases with KK-LC-1 expression in which CD8 T cells infiltrated the tumor. Regardless of the HLA class I expression or the PD-L1 expression, the KK-LC-1 expression in squamous cell lung cancer could not be detected as a significant prognostic factor. Furthermore, considering the polarity of the cancer tissue as epithelium, staining of KK-LC-1 tended to be strong in the area corresponding to the basal side of the tumor tissue. The Ki-67 expression was frequently observed in cancer cells on the basal side, which was consistent with the KK-LC-1 expression in representative four cases with KK-LC-1-positive squamous cell lung cancer.

Conclusions: Our results indicated that lung squamous cell cancer patients with KK-LC-1 expression and the tumor infiltrating CD8 T cells might exhibit better prognosis. KK-LC-1 might be highly expressed in cancer cells with high proliferative capacity. Larger cohort analysis is still required for further elucidation and validation of the results of this study.

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References

Shigematsu Y, Hanagiri T, Shiota H, Kuroda K, Baba T, Mizukami M . Clinical significance of cancer/testis antigens expression in patients with non-small cell lung cancer. Lung Cancer. 2009; 68(1):105-10. DOI: 10.1016/j.lungcan.2009.05.010. View

Stevanovic S, Pasetto A, Helman S, Gartner J, Prickett T, Howie B . Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 2017; 356(6334):200-205. PMC: 6295311. DOI: 10.1126/science.aak9510. View

Chiba T, Ohtani H, Mizoi T, Naito Y, Sato E, Nagura H . Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer follow-up period in human colorectal carcinoma: possible association with suppression of micrometastasis. Br J Cancer. 2004; 91(9):1711-7. PMC: 2410024. DOI: 10.1038/sj.bjc.6602201. View

Fukuyama T, Hanagiri T, Takenoyama M, Ichiki Y, Mizukami M, So T . Identification of a new cancer/germline gene, KK-LC-1, encoding an antigen recognized by autologous CTL induced on human lung adenocarcinoma. Cancer Res. 2006; 66(9):4922-8. DOI: 10.1158/0008-5472.CAN-05-3840. View

Takahashi Y, Fukuyama T, Futawatari N, Ichiki Y, Ohmiya H, Chuman M . Expression of Kita-Kyushu Lung Cancer Antigen-1 as Detected by a Novel Monoclonal Antibody in Gastric Cancer. Anticancer Res. 2019; 39(11):6259-6263. DOI: 10.21873/anticanres.13835. View

Jin S, Cao S, Li J, Meng Q, Wang C, Yao L . Cancer/testis antigens (CTAs) expression in resected lung cancer. Onco Targets Ther. 2018; 11:4491-4499. PMC: 6078192. DOI: 10.2147/OTT.S159491. View

Reck M, Rodriguez-Abreu D, Robinson A, Hui R, Csoszi T, Fulop A . Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016; 375(19):1823-1833. DOI: 10.1056/NEJMoa1606774. View

Rakaee M, Kilvaer T, Dalen S, Richardsen E, Paulsen E, Hald S . Evaluation of tumor-infiltrating lymphocytes using routine H&E slides predicts patient survival in resected non-small cell lung cancer. Hum Pathol. 2018; 79:188-198. DOI: 10.1016/j.humpath.2018.05.017. View

Paret C, Simon P, Vormbrock K, Bender C, Kolsch A, Breitkreuz A . CXorf61 is a target for T cell based immunotherapy of triple-negative breast cancer. Oncotarget. 2015; 6(28):25356-67. PMC: 4694836. DOI: 10.18632/oncotarget.4516. View

10.

Borghaei H, Paz-Ares L, Horn L, Spigel D, Steins M, Ready N . Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(17):1627-39. PMC: 5705936. DOI: 10.1056/NEJMoa1507643. View

11.

Ichiki Y, Taira A, Chikaishi Y, Matsumiya H, Mori M, Kanayama M . Prognostic factors of advanced or postoperative recurrent non-small cell lung cancer targeted with immune check point inhibitors. J Thorac Dis. 2019; 11(4):1117-1123. PMC: 6531735. DOI: 10.21037/jtd.2019.04.41. View

12.

Bour-Jordan H, Esensten J, Martinez-Llordella M, Penaranda C, Stumpf M, Bluestone J . Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family. Immunol Rev. 2011; 241(1):180-205. PMC: 3077803. DOI: 10.1111/j.1600-065X.2011.01011.x. View

13.

Ichiki Y, Shigematsu Y, Baba T, Shiota H, Fukuyama T, Nagata Y . Development of adoptive immunotherapy with KK-LC-1-specific TCR-transduced γδT cells against lung cancer cells. Cancer Sci. 2020; 111(11):4021-4030. PMC: 7648040. DOI: 10.1111/cas.14612. View

14.

Kondo Y, Fukuyama T, Yamamura R, Futawatari N, Ichiki Y, Tanaka Y . Detection of KK-LC-1 Protein, a Cancer/Testis Antigen, in Patients with Breast Cancer. Anticancer Res. 2018; 38(10):5923-5928. DOI: 10.21873/anticanres.12937. View

15.

Hanagiri T, Shigematsu Y, Kuroda K, Baba T, Shiota H, Ichiki Y . Prognostic implications of human leukocyte antigen class I expression in patients who underwent surgical resection for non-small-cell lung cancer. J Surg Res. 2012; 181(2):e57-63. DOI: 10.1016/j.jss.2012.07.029. View

16.

Campo M, Graham S, Cortese M, Ashrafi G, Araibi E, Dornan E . HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells. Virology. 2010; 407(1):137-42. DOI: 10.1016/j.virol.2010.07.044. View

17.

Shida A, Futawatari N, Fukuyama T, Ichiki Y, Takahashi Y, Nishi Y . Frequent High Expression of Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) in Gastric Cancer. Anticancer Res. 2015; 35(6):3575-9. View

18.

Juneja V, McGuire K, Manguso R, LaFleur M, Collins N, Nicholas Haining W . PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J Exp Med. 2017; 214(4):895-904. PMC: 5379970. DOI: 10.1084/jem.20160801. View

19.

Ichiki Y, Matsumiya H, Mori M, Kanayama M, Nabe Y, Taira A . Predictive factors of postoperative survival among patients with pulmonary neuroendocrine tumor. J Thorac Dis. 2019; 10(12):6912-6920. PMC: 6344740. DOI: 10.21037/jtd.2018.11.115. View

20.

Herbst R, Baas P, Kim D, Felip E, Perez-Gracia J, Han J . Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015; 387(10027):1540-1550. DOI: 10.1016/S0140-6736(15)01281-7. View