Institute of Molecular and Cellular Biology

Chien-Chung Chang, Ph.D.

Assistant Professor

Laboratory of Cancer Immunology

Institute of Molecular and Cellular Biology

National Tsing Hua University

101 Sec. 2 Kuang Fu Road

Hsinchu, Taiwan 30013

 

Phone: 03-574-2475

Fax: 03-571-5934

E-Mail: ccchang@life.nthu.edu.tw

 

Current research interests

Publications

Patents

Why can cancer grows in the host with a competent immune system? Do cancer cells evolve strategies to evade host tumor-specific immune responses? How are the gene products of major histocompatibility complex (MHC), the components of antigen processing machinery, and immune checkpoint signaling manipulated by malignant cells to establish an immunosuppressive tumor microenvironment in order to avoid attack by T and NK cells? How does genotoxic stress contribute to NKG2D-related innate self/non-self discrimination imbalance, which impairs cancer immune surveillance by NK cells? How can we make cancer immunotherapy more effective for patients by counteracting multiple cancer immune resistance mechanisms? These questions are addressed in the Chang Laboratory using a number of state-of-the-art immunological, molecular biological, biochemical and structural biological approaches.   

Pan, Y.-G., Chang, C.-C.* (2019) Artificial antigen presentosomes for T cell activation. Methods Mol. Biol., in press

 

Wang, S.-C., Wu, C.-T., Wu, D.-Y., Chen, C.G., Chang, K.-M., Chang, C.-C.* (2019) The impact of the epigenetic cancer drug azacitidine on host immunity: the role of myelosuppression, iron overload and tp53 mutations in a zebrafish model. Cancers. 11(9): 1294. doi: 10.3390/cancers11091294

 

Lei, W.-Y., Hsiung, S.-C., Wen, S.-H., Hsieh, C.-H., Chen, C.-L., Wallace, C.G., Chang, C.-C.*, Liao, S.-K.* (2018) Total HLA class I antigen loss with the downregulation of antigen-processing machinery components in two newly established sarcomatoid hepatocellular carcinoma cell lines. J. Immunol. Res. 2018: 8363265. doi: 10.1155/2018/8363625

 

Chen, J.L.-Y., Chang, C.-C., Huang, Y.-S., Kuo, H.-Y., Chen, T.-Y., Wang, C.-W. Kuo, S.-H., Lin, Y.-L. (2018) Persistently elevated soluble MHC class I polypeptide-related sequence A and transforming growth factor-β1 levels are poor prognostic factors in head and neck squamous cell carcinoma after definitive chemoradiotherapy. PLoS ONE 13(8): e0202224.

 

Guo, D., Xu, Q., Pabla, S., Koomen, J., Biddinger, P., Sharma, A., Pabla, S., Pacholczyk, R., Chang, C.-C., Friedrich, K., Mohammed, K., Smallridge, R.C., Copland, J.A., She, J.-X., Weinberger, P.M. (2018) Cytokeratin-8 in anaplastic thyroid carcinoma: more than a simple structural cytoskeletal protein. Int. J. Mol. Sci. 19:577. doi: 10.3390/ijms19020577

 

Liang, Y.-H., Lin, Y.-C., Chen, K.-H., Kao, C.-H., Cheng, A.-L., Yeh, K.-H., Chang, C.-C.* (2017) HLA and NKG2D ligand abnormalities and IFN-g unresponsiveness in human colorectal carcinoma cell lines. Proceedings of the American Association for Cancer Research 58:1135-1136

 

Kuo, H.-Y., Lin, Y.-C., Guo, J.-C., Huang, T.-C., Lin, C.-C., Yeh, K.-H., Cheng, A.-L., Hsu, C.-H., Chang, C.-C.* (2016) The association of plasma soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA) level with the pathological complete response (pCR) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) Ann. Oncol. 27(suppl 9)

 

Yeh, C.-H., Kumar, V., Moyano, D.-R., Wen, S.-H., Parashar, V., Hsiao, S.-H., Srivastava, A., Saxena, P.S., Huang, K.-P., Chang, C.-C.*, Chiu, P.-W.* (2016) High-performance and high-sensitivity applications of graphene transistors with self-assembled monolayers. Biosens. Bioelectron. 77:1008-1015

 

Chang, C.-C.*, Pirozzi, G., Wen, S.-H., Chung, I.-H., Chiu, B.-L., Errico, S., Luongo, M., Lombardi, M.L., and Ferrone, S. (2015) Multiple structural and epigenetic defects in the human leukocyte antigen class I antigen presentation pathway in a recurrent metastatic melanoma following immunotherapy. J. Biol. Chem. 290:26562-26575

 

Qiu, Y.-Q., Yang, C.-W., Lee, Y.-Z., Yang, R.-B., Lee, C.-H., Hsu, H.-Y., Chang, C.-C. Lee, S.-J. (2015) Targeting a ribonucleoprotein complex containing caprin-1 protein and the c-Myc mRNA suppresses tumor growth in mice: an identification of a novel oncotarget. Oncotarget 6:2148-2163

 

Wu, M.-S., Li, C.-H., Ruppert, J.G., Chang, C.-C.* (2013) Cytokeratin 8-MHC class I interactions: a potential novel immune escape phenotype by a lymph node metastatic carcinoma cell line. Biochem. Biophys. Res. Commun. 441:618-623

 

Chiu, B.-L., Li, C.-H, Chang, C.-C.* (2013) Selective modulation of MHC class II chaperons by a novel IFN-g-inducible class II transactivator variant in lung adenocarcinoma A549 cells. Biochem. Biophys. Res. Commun. 440:190-195

 

Luo, W.-Y., Lin S.-Y., Lo, K.-W., Lu, C.-H., Hung, C.-L., Chen, C.-Y., Chang, C.-C., and Hu, Y.-C. (2013) Adaptive immune responses elicited by baculovirus and impacts on subsequent transgene expression in vivo. J. Virol. 87:4965-4973.

 

Lin, H.-C., Wang, S.-C., Chen, C. G.-S, Chang, M.-C., Wang, W.-T., Su, N.-W, Cheng, H.-I., Lin, J., Chang, Y.-F., Hsieh, R.-K., Chang, C.-C., Hwang, Y., Lim, K.-H., and Kuo, Y.-Y. (2012) Mutation and lineage analysis of DNMT3A in BCR-ABL1-negative chronic myeloproliferative neoplasms. Int. J. Gerontol. 7:186-188

 

Hsieh, C.-H., Hsu, Y.-J., Chang, C.-C., Liu, H.-C., Chuang, K.-L., Chuang, C.-K., Pang, S.-T., Hasumi, K., Ferrone, S. and Liao, S.-K. (2009) Total HLA class I loss in a sarcomatoid renal cell carcinoma cell line caused by the coexistence of distinct mutations in the two encoding β₂-microglobulin gene. Cancer Immunol. Immunother. 58:395-408.

 

Wongsena, W., Sconocchia, G., Cho, H.-S., Chang, C.-C., Wang, X., Klumkrathok, K., Ferrone, S., and Leelayuwat, C. (2008) Production and characterization of monoclonal antibodies against major histocompatibility complex class I chain-related gene A. Tissue Antigens. 72:431-40.

 

Sangrouber, D, Marcou, C., Le Discorde, M., Chang, C.-C., Carosella, E.D. and Moreau, P. (2007) Cellular co-localization of intron 4–containing mRNA and HLA-G soluble protein in melanoma analyzed by fluorescence in situ hybridization. J. Immunol. Methods. 326: 54-62.

 

Chang, C.-C. and Ferrone, S. (2007) Immune selective pressure and HLA class I antigen defects in malignant lesions. Cancer Immunol. Immunother. 56: 227-236.

 

Chang, C.-C. and Ferrone, S. (2006) NK cell activating ligands on human malignant cells: molecular and functional defects and potential clinical relevance. Semin. Cancer Biol. 16: 383-392.

 

Chang, C.-C., Ogino, T, Mullin, D.W., Yamshchikov, G.V., Bandoh N., Slingluff, C.L. Jr., and Ferrone, S. (2006) Defective HLA class I-associated antigen presentation caused by a novel β2-microglobulin loss-of-function in melanoma cells. J. Biol. Chem. 281: 18763-18773.

 

Shen, C., Chang, C.-C., Zhang, J., Guo, W., Xia, L., Meng, F., and Xie, W. (2006) Structural and functional characterization of peptide-β2m fused HLA-A2/MART127-35 complexes. Biochem. Biophys. Res. Commun. 342: 57-65.

 

Chang, C.-C., Hernandez-Guzman, F.G., Luo, W., Wang, X., Ferrone, S., and Ghosh, D. (2005) Structural basis of antigen mimicry in a clinically relevant melanoma antigen system. J. Biol. Chem. 280: 41546-41552.

 

Yan, W.-H., Lin, A.-F., Chang, C.-C., and Ferrone, S. (2005) Induction of HLA-G expression in a melanoma cell line OCM-1A following the treatment with 5-aza-2'-deoxycytidine. Cell Res. 15: 523-531.

 

Yamshchikov, G.V., Mullins, D.W., Chang, C.-C., Ogino, T., Thompson, L., Presley, J., Galavotti, H., Aquila, W., Deacon, D., Ross, W., Patterson, J.W., Engelhard, V.H., Ferrone, S., and Slingluff, C.L., Jr. (2005) Sequential immune escape and shifting of T cell responses in a long-term survivor of melanoma. J. Immunol. 174: 6863-6871.

 

Chang, C.-C., Campoli, M., and Ferrone, S. (2005) Classical and non-classical HLA class I antigen and NK cell activating ligand changes in malignant cells: current challenges and future directions. Adv. Cancer Res. 93: 189-234.

 

Chang, C.-C., Campoli, M., Restifo, N.P., Wang, X., and Ferrone, S. (2005) Immune selection of hot-spot β2-microglobulin gene mutations, HLA-A2 allospecificity loss and antigen processing machinery component downregulation in melanoma cells derived from recurrent metastases following immunotherapy. J. Immunol. 174: 1462-1471.

 

Chang, C.-C., Campoli, M., Luo, W., Zhao, W., Zanker, K.S., and Ferrone, S. (2004) Immunotherapy of melanoma targeting human high molecular weight-melanoma associated antigen: potential role of non-immunological mechanisms. Ann. NY Acad. Sci. 1028: 340-350.

 

Campoli, M., Chang, C.-C., Kageshita, T., Wang, X., McCarthy, J.B., and Ferrone, S. (2004) Human High Molecular Weight-Melanoma Associated Antigen (HMW-MAA): a melanoma cell surface chondroitin sulfate proteoglycan (MCSP) with biological and clinical significance. Crit. Rev. Immunol. 24: 267-296.

 

Chang, C.-C., Campoli, M., and Ferrone, S. (2004) HLA class I antigen expression in malignant cells: why does it not always correlate with CTL-mediated lysis? Curr. Opin. Immunol. 16: 644-650.

 

Campoli, M., Chang, C.-C., Oldford, S.A., Edgecombe, A.D., Drover, S., and Ferrone, S. (2004) HLA antigen changes in malignant tumors of mammary epithelial origin: molecular mechanisms and clinical implications. In: Breast Disease. Immunology of Breast Cancer, Wei, W.Z., Lopez, D.M. (eds), Amsterdam: IOS Press, 20: 105-125.

 

Pirozzi, G., Chang, C.-C., Errico, S., Curci, A., Luongo, V., Paino, F., Di Gennaro, E., Ferrone, S., and Lombardi, M.L. (2004) Molecular defects underlying HLA class I antigen abnormalities in melanoma cells. In: HLA 2004:  Immunobiology of the human MHC. Hansen J., Dupont, B. (eds.), Vol. I, pp. IHWG Press, Seattle, Washington.

 

Campoli, M., Chang, C.-C., Wang, X., and Ferrone, S. (2003) HLA class I antigen processing machinery and HLA class I antigen derived peptide complex defects in tumor cell escape.  In: Cancer Immunotherapy at the crossroad – How tumors evade immunity and what can be done, Finke, J.H., Bukowski, R.M. (eds). Totowa: The Humana Press Inc., pp. 3-34.

 

Chang, C.-C., Campoli, M., and Ferrone, S. (2003) HLA class I defects in malignant lesions: what have we learned? Keio J. Med. 52: 220-229.

 

Chang, C.-C., Murphy, S.P., and Ferrone, S. (2003) Differential in vivo and in vitro HLA-G expression in melanoma cells: potential mechanisms. Hum. Immunol. 64: 1057-1063.

 

Chang, C.-C. and Ferrone, S. (2003) HLA-G in melanoma: can the current controversies be solved? Semin. Cancer Biol. 13: 361-369.

 

Campoli, M., Chang, C.-C., and Ferrone, S. (2002) HLA class I antigen loss, tumor immune escape and immune selection. Vaccine. 20 Suppl 4: A40-A45.

 

Pende, D., Rivera, P., Marcenaro, S., Chang, C.-C., Biassoni, R., Kubin, M., Cosman, D., Ferrone, S., Moretta, L., and Moretta, A. (2002) Major histocompatibility complex class I-related chain A and UL16-binding protein  expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity. Cancer Res. 62: 6178-6186.

 

Chang, C.-C. and Ou, J.T. (2002) Excess production of interleukin-12 subunit p40 stimulated by the virulence plasmid of Salmonella enterica serovar Typhimurium in the early phase of infection in the mouse. Microb. Pathog. 32: 15-25.

 

Hor, L.-I., Chang, Y.-K., Chang, C.-C., Lei, H.-Y. and Ou, J.T. (2000) Mechanism of high susceptibility of iron-    overloaded mouse to Vibrio vulnificus infection. Microbiol. Immunol. 44: 871-878.

 

 

Wu, M.-S., Chiu, P.-L., Li, C.-H., Ruppert, J., Chang, C.-C. (2012) Investigating the differential immunoresistance mechanisms by two subpopulations of a metastatic carcinoma cell line. The 5th Annual NHRI-NTHU Joint Conference on Biomedicine.

 

Li, C.-H., Chang, Y.-T., Chen, F.-C., Chang, L.-Y., Chang, C.-C. (2011) Cigarette smoke-induced MHC class II downregulation through post-transcriptional inactivation of CIITA. Cold Spring Harbor Asia Conferences on Infection and Immunity. Shuzhou, China.

 

Chang, L.-Y., Li, C.-H., Wen, H.-S., Chang, C.-C. (2011) MHC class II downregulation and pulmonary fibrosis gene response induced in the bronchial epithelial cell line BEAS-2B exposed to cigarette smoke compounds. The 4th Annual NHRI-NTHU Joint Conference on Biomedicine.

 

Peh, J.-H., Liu, M.-Y., Chang, C.-C. (2010) Investigating the Zebrafish Novel Immune-type Receptor-9 System. The 2010 Taiwan Zebrafish Symposium. Zhunan, Taiwan, R.O.C.

 

Chang, C.-C. (2010) Breast cancer immunoresistance: role of MHC-associated defects and leptin signaling. BIT’s 3^rd World Cancer Congress-Breast Cancer Conference, Shanghai, China.

 

Lin, M.-H., Chang, Y.-T., Chang, C.-C. (2009) Functional Characterization of Zebrafish Major Histocompatibility Complex class I Molecules. Poster. The Twenty-fourth Joint Annual Conference of Biomedical Sciences, Taipei, Taiwan, R.O.C

 

Chang, C.-C. (2008) MHC-associated antigen processing machinery and escape of human tumors from T cell recognition: what have we learned? The lst Annual NHRI-NTHU Joint Conference on Biomedicine.

 

Chang, C.-C., Luo, W., Wang, X., Ferrone, S., and Ghosh, D. (2006) Structural basis of tumor antigen mimicry by a mimotope isolated from a phage display peptide library. J. Immunol. 176: S261. The American Association of Immunologists 2006 Annual Meeting, Boston, MA.

 

Chang, C.-C. and Ferrone, S. (2004) HER2/neu-targeted breast cancer immunotherapy: a hybrid protein approach. The Susan G. Komen Breast Cancer Foundation 2004 Mission Conference, New York, NY.

 

Yamshchikov, G.V., Thompson, L., Mullins, D.W., Ferrone, S., Ogino, T., Chang, C.-C., Galavotti, H., Aquila, W., Deacon, D., Ross, W., Patterson, J.W., Engelhard, V.H., and Slingluff, C.L., Jr. (2003) Immun escape, immune editing, and immune adaptation in a long-term survivor of metastatic melanoma. The 18th Annual Scientific Meeting of the International Society for Biological Therapy of Cancer, Bethesda, MD. J. Immunother. 26: S45, 2003

 

Chang, C.-C., Pirozzi, G., Lombardi, M.L., and Ferrone, S. (2003) Identification of a tapasin gene mutation in a human melanoma cell line with HLA class I antigen downregulation. The 90th Annual Meeting of the American Association of Immunologists, Denver, CO. FASEB J. 17: C326, 2003.

 

Bandoh N., Chang, C.-C., Cho, H.S., Wang, X, Ogino, T., Harabuchi, Y., Whiteside, T.L., and Ferrone, S. (2003) HLA class I antigen downregulation in human head and neck squamous cell carcinoma cell lines: Role of antigen processing machinery defects. The 94th Annual Meeting of the American Association for Cancer Research, Washington, D.C. Proc. Am. Assoc. Cancer Res. 44: 770, 2003.

 

Pirozzi, G., Chang, C.-C., Errico, S., Curci, A., Luongo, V., Paino, F., DiGennaro, E., Ferrone, S. and Lombardi, M.L. (2002) Molecular defects underlying HLA class I antigen abnormalities in melanoma cells. The 13th International Histocompatibility Workshop and Congress, Seattle, WA. Tissue Antigens. 59: S90, 2002.

 

Chang, C.-C., Bankert, R.B. and Ferrone, S. (2002) Multiple molecular lesions in a human lung carcinoma cell line with HLA antigen loss. The 13th International Histocompatibility Workshop and Congress, Seattle, WA. Tissue Antigens. 59: S84-S85, 2002.

 

Chang, C.-C. and Ou, J.T. (1999) Excess stimulation of p40, a subunit of interleukin 12, production by the Salmonella typhimurium virulence plasmid. The 99th General Meeting of American Society for Microbiology, Chicago, IL.

"Peptides for stimulating an immune response against melanoma", U.S.A. US 7,887,822 B2

 

“Antigen presenting composition and use thereof”, U.S.A. US 8,834,889 B2. 

                            

“兩單元仿生人工胜肽抗原呈現平台”R.O.C.  TW201309727.

Conference/symposium proceedings (selected)