Identification of tumor antigens in malignant mesothelioma

Our plain-English summary of Identification of tumor antigens in malignant mesothelioma, by Y.R. Kim, M.H. Song, J.W. Lee, et al (Oncology Letters, 2017).

The study

• Authors: Y.R. Kim, M.H. Song, J.W. Lee, J.H. Bae, J.E. Kim, D.M. Kang, S.Y. Lee
• Journal: Oncology Letters
• Published: 2017;14(4):4557-4562
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Serological analysis of recombinant tumor cDNA expression library (SEREX) is a powerful and widely used method to explore the cancer immune environment. In the present study, immunoscreening of normal testicular tissues and malignant mesothelioma (MM) cancer MSTO-211H cell line cDNA libraries with sera from 5 MM patients led to the isolation of 16 independent antigens, which were designated 'Korea Pusan-Malignant Mesothelioma' (KP-MM)-1 to -16. In total, 3/16 antigens were identified using the results of previous SEREX analyses, and 13 were newly identified. Of these, KP-MM-8, which was subsequently identified as amyotrophic lateral sclerosis 2 chromosome region candidate 11, was shown to be tissue-restricted. Reverse transcription-polymerase chain reaction demonstrated KP-MM-8 to be expressed strongly only in the normal testis, and weakly in the spleen, prostate, ovary, heart and skeletal muscle. In addition, KP-MM-8 mRNA was identified in MM cell lines, and in various other cancer cell lines, including MM (3/4), lung cancer (5/7), melanoma (5/7) and liver cancer (5/5) cell lines. Additionally, 2/16 antigens (KP-MM-2 and KP-MM-6) exclusively reacted with sera from cancer patients. However, KP-MM-8 reacted with 1 of 8 MM sera. Notably, 8/8 patients with MM and 8/8 normal individuals exhibited antibodies reactive to KP-MM-5, which was identified as cell division cycle 25B, a known oncogene. Overall, this data suggests that KP-MM-8 may be considered as a cancer/testis-like antigen and KP-MM-5 as an immunogenic tumor antigen in MM patients.

In plain English

This Korean laboratory study looked for tumor antigens, proteins in malignant mesothelioma that the immune system recognizes. The authors screened gene libraries from normal testis and a mesothelioma cell line (MSTO-211H) with serum from 5 mesothelioma patients. They identified 16 candidate antigens, named KP-MM-1 to KP-MM-16. Thirteen of these had not been reported before by this method. Tests of normal tissues found that the messenger RNA of one antigen, KP-MM-8 (the gene ALS2CR11), was strongly expressed only in the testis, and weakly in five other tissues. This mRNA was also detected in 3 of 4 mesothelioma cell lines and several other cancer cell lines. However, antibodies to KP-MM-8 appeared in only 1 of 8 patients' sera and none of 8 healthy donors' sera. All 8 patients and all 8 healthy donors had antibodies to KP-MM-5 (CDC25B). The authors concluded KP-MM-8 may be a cancer/testis-like antigen and KP-MM-5 an immunogenic tumor antigen in mesothelioma patients. They noted the limited number of patient sera and said the healthy donors' strong reaction to KP-MM-5 needs more study. The study did not examine asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study: screening of gene (cDNA) expression libraries with patient sera (SEREX), gene expression testing in tissues and cell lines, and antibody testing of sera
• Who was studied: Sera from 8 malignant mesothelioma patients and 8 healthy donors, collected February 2008 to December 2013 at Pusan National University Hospital (Yangsan, Korea). Sera from 5 of the patients were used for the library screening; per Table I, these included patients with malignant pleural and malignant peritoneal mesothelioma. The study also used normal tissue RNA and a range of human cancer cell lines.
• Exposure: Not studied; the article does not report asbestos or other exposures for the patients
• Main results:
  • Screening found 31 immunogenic clones, from which 16 candidate antigens were identified. Of the 16, 3 had previously been identified by SEREX in other tumor types and 13 were new.
  • In normal tissues, RT-PCR showed that KP-MM-8 (ALS2CR11) mRNA was strongly expressed only in the testis and weakly in the spleen, prostate, ovary, heart and skeletal muscle
  • RT-PCR detected ALS2CR11 mRNA in 3 of 4 mesothelioma cell lines, 5 of 7 lung cancer cell lines, 5 of 7 melanoma cell lines and 5 of 5 liver cancer cell lines. It was not expressed in the colon cancer, renal cancer or leukemia cell lines.
  • Antibodies to KP-MM-8 were found in 1 of 8 mesothelioma patients' sera and in none of the 8 healthy donors' sera
  • Antibodies to KP-MM-6 were found in 2 of 8 mesothelioma patients' sera and in none of the 8 healthy donors' sera
  • All 8 mesothelioma patients and all 8 healthy donors showed high reactivity to KP-MM-5 (CDC25B). In one patient and one healthy donor, reactivity was still seen at a one-million-fold serum dilution.
• The authors' conclusion: The authors concluded that KP-MM-8 may be considered a cancer/testis-like antigen and KP-MM-5 an immunogenic tumor antigen in mesothelioma patients
• Limitations the authors state:
  • The antibody result for KP-MM-8 was based on a limited number of patient serum samples; more samples are needed
  • Sera from healthy donors also reacted strongly to KP-MM-5, which the authors said requires further investigation

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Lung Cancer.

Related studies

• Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies — G.L. Beatty, A.R. Haas, et al. (2014)
• Tumor-infiltrating dendritic cells exhibit defective cross-presentation of tumor antigens, but is reversed by chemotherapy — A.M. McDonnell, W.J. Lesterhuis, et al. (2015)
• Immunoperoxidase localization of keratin proteins, carcinoembryonic antigen, and factor VIII in adenomatoid tumors: evidence for a mesothelial derivation — J.W. Said, G. Nash, et al. (1982)
• Human mesotheliomas contain the simian virus-40 regulatory region and large tumor antigen DNA sequences — H.I. Pass, J.S. Donington, et al. (1998)
• Distribution of the carbohydrate antigens, DU-PAN-2 and CA19-9, in tumors of the lung — G. Ohshio, K. Yamaki, et al. (1995)
• A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma — J. Lai, Z. Zhou, et al. (2016)

Browse more research in Oncology Letters, or return to medical research.