FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells
Background. Immune checkpoint inhibitors (ICIs) have rapidly revolutionized colorectal cancer (CRC) treatment, but resistance caused by the heterogeneous tumor microenvironment (TME) still presents a challenge. Therefore, it is necessary to characterize TME immune infiltration and explore new target...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/3129765 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832549212260139008 |
|---|---|
| author | Wenping Lian Zhongquan Wang Yajie Ma Yalin Tong Xinyu Zhang Huifang Jin Shuai Zhao Ruijing Yu Shaotan Ju Xinyun Zhang Xiaona Guo Tao Huang Xianfei Ding Mengle Peng |
| author_facet | Wenping Lian Zhongquan Wang Yajie Ma Yalin Tong Xinyu Zhang Huifang Jin Shuai Zhao Ruijing Yu Shaotan Ju Xinyun Zhang Xiaona Guo Tao Huang Xianfei Ding Mengle Peng |
| author_sort | Wenping Lian |
| collection | DOAJ |
| description | Background. Immune checkpoint inhibitors (ICIs) have rapidly revolutionized colorectal cancer (CRC) treatment, but resistance caused by the heterogeneous tumor microenvironment (TME) still presents a challenge. Therefore, it is necessary to characterize TME immune infiltration and explore new targets to improve immunotherapy. Methods. The compositions of 64 types of infiltrating immune cells and their relationships with CRC patient clinical characteristics were assessed. Differentially expressed genes (DEGs) between “hot” and “cold” tumors were used for functional analysis. A prediction model was constructed to explore the survival of CRC patients treated with and without immunotherapy. Finally, fatty acid-binding protein (FABP6) was selected for in vitro experiments, which revealed its roles in the proliferation, apoptosis, migration, and immunogenicity of CRC tissues and cell lines. Results. The infiltration levels of several immune cells were associated with CRC tumor stage and prognosis. Different cell types showed the synergistic or antagonism infiltration patterns. Enrichment analysis of DEGs revealed that immune-related signaling was significantly activated in hot tumors, while metabolic process pathways were altered in cold tumors. In addition, the constructed model effectively predicted the survival of CRC patients treated with and without immunotherapy. FABP6 knockdown did not significantly alter tumor cell proliferation, apoptosis, and migration. FABP6 was negatively correlated with immune infiltration, and knockdown of FABP6 increased major histocompatibility complex (MHC) class 1 expression and promoted immune-related chemokine secretion, indicating the immunogenicity enhancement of tumor cells. Finally, knockdown of FABP6 could promote the recruitment of CD8+ T cells. Conclusion. Collectively, we described the landscape of immune infiltration in CRC and identified FABP6 as a potential immunotherapeutic target for treatment. |
| format | Article |
| id | doaj-art-08837758ee0949ebbfdf4c09763d17c5 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-08837758ee0949ebbfdf4c09763d17c52025-02-03T06:11:51ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/3129765FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer CellsWenping Lian0Zhongquan Wang1Yajie Ma2Yalin Tong3Xinyu Zhang4Huifang Jin5Shuai Zhao6Ruijing Yu7Shaotan Ju8Xinyun Zhang9Xiaona Guo10Tao Huang11Xianfei Ding12Mengle Peng13Department of Clinical LaboratoryDepartment of Clinical LaboratoryDepartment of NeurologyDepartment of DigestionDepartment of Medical AffairDepartment of Blood TransfusionDepartment of Clinical LaboratoryDepartment of Clinical LaboratoryDepartment of Clinical LaboratoryDepartment of Anorectal SurgeryMedical SchoolMedical SchoolMedical SchoolDepartment of Clinical LaboratoryBackground. Immune checkpoint inhibitors (ICIs) have rapidly revolutionized colorectal cancer (CRC) treatment, but resistance caused by the heterogeneous tumor microenvironment (TME) still presents a challenge. Therefore, it is necessary to characterize TME immune infiltration and explore new targets to improve immunotherapy. Methods. The compositions of 64 types of infiltrating immune cells and their relationships with CRC patient clinical characteristics were assessed. Differentially expressed genes (DEGs) between “hot” and “cold” tumors were used for functional analysis. A prediction model was constructed to explore the survival of CRC patients treated with and without immunotherapy. Finally, fatty acid-binding protein (FABP6) was selected for in vitro experiments, which revealed its roles in the proliferation, apoptosis, migration, and immunogenicity of CRC tissues and cell lines. Results. The infiltration levels of several immune cells were associated with CRC tumor stage and prognosis. Different cell types showed the synergistic or antagonism infiltration patterns. Enrichment analysis of DEGs revealed that immune-related signaling was significantly activated in hot tumors, while metabolic process pathways were altered in cold tumors. In addition, the constructed model effectively predicted the survival of CRC patients treated with and without immunotherapy. FABP6 knockdown did not significantly alter tumor cell proliferation, apoptosis, and migration. FABP6 was negatively correlated with immune infiltration, and knockdown of FABP6 increased major histocompatibility complex (MHC) class 1 expression and promoted immune-related chemokine secretion, indicating the immunogenicity enhancement of tumor cells. Finally, knockdown of FABP6 could promote the recruitment of CD8+ T cells. Conclusion. Collectively, we described the landscape of immune infiltration in CRC and identified FABP6 as a potential immunotherapeutic target for treatment.http://dx.doi.org/10.1155/2022/3129765 |
| spellingShingle | Wenping Lian Zhongquan Wang Yajie Ma Yalin Tong Xinyu Zhang Huifang Jin Shuai Zhao Ruijing Yu Shaotan Ju Xinyun Zhang Xiaona Guo Tao Huang Xianfei Ding Mengle Peng FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells Journal of Immunology Research |
| title | FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells |
| title_full | FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells |
| title_fullStr | FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells |
| title_full_unstemmed | FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells |
| title_short | FABP6 Expression Correlates with Immune Infiltration and Immunogenicity in Colorectal Cancer Cells |
| title_sort | fabp6 expression correlates with immune infiltration and immunogenicity in colorectal cancer cells |
| url | http://dx.doi.org/10.1155/2022/3129765 |
| work_keys_str_mv | AT wenpinglian fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT zhongquanwang fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT yajiema fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT yalintong fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT xinyuzhang fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT huifangjin fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT shuaizhao fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT ruijingyu fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT shaotanju fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT xinyunzhang fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT xiaonaguo fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT taohuang fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT xianfeiding fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells AT menglepeng fabp6expressioncorrelateswithimmuneinfiltrationandimmunogenicityincolorectalcancercells |