The loss of neoantigens is an important reason for immune escape in multiple myeloma patients with high intratumor heterogeneity
Abstract Objectives Intratumor heterogeneity (ITH) is an important factor for clinical outcomes in patients with multiple myeloma (MM). High ITH has been proven to be a key reason for tumor immune escape and treatment resistance. Neoantigens are thought to be associated with ITH, but the specific co...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.6721 |
| _version_ | 1797371940997955584 |
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| author | Yue Wang Jiadai Xu Tianwei Lan Chi Zhou Peng Liu |
| author_facet | Yue Wang Jiadai Xu Tianwei Lan Chi Zhou Peng Liu |
| author_sort | Yue Wang |
| collection | DOAJ |
| description | Abstract Objectives Intratumor heterogeneity (ITH) is an important factor for clinical outcomes in patients with multiple myeloma (MM). High ITH has been proven to be a key reason for tumor immune escape and treatment resistance. Neoantigens are thought to be associated with ITH, but the specific correlation and functional basis for this remains unclear. Methods We study this question through the whole‐exome sequencing (WES) data from 43 high ITH newly diagnosed MM patients in our center. Mutant allele tumor heterogeneity (MATH) was conducted to quantify ITH. The cutoff value for high intratumor heterogeneity was determined by comparing MATH of different kinds of tumors. NeoPredPipe was performed to predict neoantigens and binding affinity. Results Compared to other tumors, MM has a relatively low tumor mutation burden but a high ITH. Patients with high MATH had significantly shorter progression‐free survival times than those with low MATH (p = 0.001). In high ITH samples, there is a decrease in strong‐binding neoantigens (p = 0.019). The loss of strong‐binding neoantigens is a key factor for insensitivity to therapy (p = 0.015). Loss of heterozygosity in HLA was not observed. In addition, patients with fewer neoantigens loss had higher rates of disease remission (p = 0.047). CD8 + T cells (p = 0.012) and NK cells (p = 0.011) decreased significantly in patients with high neoantigens loss rate. A prediction model based on neoantigens was built to evaluate the strength of immune escape. Conclusion The loss of strong‐binding neoantigens explains why tumors with high ITH have a higher degree of immune escape and may be feasible for deciding the clinical treatment of MM. |
| first_indexed | 2024-03-08T18:28:06Z |
| format | Article |
| id | doaj.art-cfbac5b2ccdd4be29f82009d37a0434d |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T18:28:06Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-cfbac5b2ccdd4be29f82009d37a0434d2023-12-30T08:53:25ZengWileyCancer Medicine2045-76342023-12-011224216512166510.1002/cam4.6721The loss of neoantigens is an important reason for immune escape in multiple myeloma patients with high intratumor heterogeneityYue Wang0Jiadai Xu1Tianwei Lan2Chi Zhou3Peng Liu4Department of Hematology, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Hematology, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Hematology, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Hematology, Zhongshan Hospital Fudan University Shanghai ChinaDepartment of Hematology, Zhongshan Hospital Fudan University Shanghai ChinaAbstract Objectives Intratumor heterogeneity (ITH) is an important factor for clinical outcomes in patients with multiple myeloma (MM). High ITH has been proven to be a key reason for tumor immune escape and treatment resistance. Neoantigens are thought to be associated with ITH, but the specific correlation and functional basis for this remains unclear. Methods We study this question through the whole‐exome sequencing (WES) data from 43 high ITH newly diagnosed MM patients in our center. Mutant allele tumor heterogeneity (MATH) was conducted to quantify ITH. The cutoff value for high intratumor heterogeneity was determined by comparing MATH of different kinds of tumors. NeoPredPipe was performed to predict neoantigens and binding affinity. Results Compared to other tumors, MM has a relatively low tumor mutation burden but a high ITH. Patients with high MATH had significantly shorter progression‐free survival times than those with low MATH (p = 0.001). In high ITH samples, there is a decrease in strong‐binding neoantigens (p = 0.019). The loss of strong‐binding neoantigens is a key factor for insensitivity to therapy (p = 0.015). Loss of heterozygosity in HLA was not observed. In addition, patients with fewer neoantigens loss had higher rates of disease remission (p = 0.047). CD8 + T cells (p = 0.012) and NK cells (p = 0.011) decreased significantly in patients with high neoantigens loss rate. A prediction model based on neoantigens was built to evaluate the strength of immune escape. Conclusion The loss of strong‐binding neoantigens explains why tumors with high ITH have a higher degree of immune escape and may be feasible for deciding the clinical treatment of MM.https://doi.org/10.1002/cam4.6721immune escapeintratumor heterogeneitymultiple myelomaneoantigentumor mutation burden |
| spellingShingle | Yue Wang Jiadai Xu Tianwei Lan Chi Zhou Peng Liu The loss of neoantigens is an important reason for immune escape in multiple myeloma patients with high intratumor heterogeneity Cancer Medicine immune escape intratumor heterogeneity multiple myeloma neoantigen tumor mutation burden |
| title | The loss of neoantigens is an important reason for immune escape in multiple myeloma patients with high intratumor heterogeneity |
| title_full | The loss of neoantigens is an important reason for immune escape in multiple myeloma patients with high intratumor heterogeneity |
| title_fullStr | The loss of neoantigens is an important reason for immune escape in multiple myeloma patients with high intratumor heterogeneity |
| title_full_unstemmed | The loss of neoantigens is an important reason for immune escape in multiple myeloma patients with high intratumor heterogeneity |
| title_short | The loss of neoantigens is an important reason for immune escape in multiple myeloma patients with high intratumor heterogeneity |
| title_sort | loss of neoantigens is an important reason for immune escape in multiple myeloma patients with high intratumor heterogeneity |
| topic | immune escape intratumor heterogeneity multiple myeloma neoantigen tumor mutation burden |
| url | https://doi.org/10.1002/cam4.6721 |
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