Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancer
Background: Despite the introduction of trastuzumab, pathologic complete response (pCR) is not attained in approximately 30–40% of Human epithelial growth factor receptor-2-positive breast cancer. Tumor-infiltrating lymphocytes (TIL) have been suggested as a predictive marker of treatment response,...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2023-02-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359231157654 |
| _version_ | 1797894107964637184 |
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| author | Junyoung Shin Baknoon Ham Jeong-Han Seo Sae Byul Lee In Ah Park Gyungyub Gong Sung-Bae Kim Hee Jin Lee |
| author_facet | Junyoung Shin Baknoon Ham Jeong-Han Seo Sae Byul Lee In Ah Park Gyungyub Gong Sung-Bae Kim Hee Jin Lee |
| author_sort | Junyoung Shin |
| collection | DOAJ |
| description | Background: Despite the introduction of trastuzumab, pathologic complete response (pCR) is not attained in approximately 30–40% of Human epithelial growth factor receptor-2-positive breast cancer. Tumor-infiltrating lymphocytes (TIL) have been suggested as a predictive marker of treatment response, albeit not always effective. We investigated the relationship between trastuzumab, docetaxel, carboplatin, and pertuzumab (TCHP) treatment and immune repertoire as a treatment response predictor. Design: In all, 35 cases were divided into two experimental groups: 10 and 25 cases in the preliminary and main experiments, respectively. In the preliminary experiment, the biopsy tissues before TCHP treatment and the surgical tissues after TCHP treatment were compared. In the main experiment, the biopsy tissues before TCHP treatment were compared according to the TCHP treatment response. Methods: The T-cell repertoire for TRA, TRB, TRG, and TRD, and B-cell repertoire for immunoglobulin heavy, immunoglobulin kappa, and immunoglobulin lambda were evaluated. Whole transcriptome sequencing was also performed. Results: In the preliminary experiment, the density and richness of the T-cell receptor (TCR) and B-cell receptor (BCR) repertoires decreased after treatment, regardless of TCHP response. In the main experiment, the Shannon’s entropy index, density, and length of CDR3 of the TCR and BCR repertoires did not differ significantly in patients who did and did not achieve pCR. The pCR and non-pCR subgroups according to the level of TILs revealed that the non-pCR/lowTIL group had a higher proportion of low-frequency clones than the pCR/lowTIL group in TRA (non-pCR/lowTIL versus pCR/lowTIL, 0.01–0.1%, 63% versus 45.3%; <0.01%, 32.9% versus 51.8%, p < 0.001) and TRB (non-pCR/lowTIL versus pCR/lowTIL, 0.01–0.1%, 26.5% versus 14.7%; <0.01%, 72.0% versus 84.1%, p < 0.001). Conclusions: The role of the diversity, richness, and density of the TCR and BCR repertoires as predictive markers for TCHP response was not identified. Compositions of low-frequency clones could be candidates for predictive factors of TCHP response; however, validation studies and further research are necessary. |
| first_indexed | 2024-04-10T07:03:34Z |
| format | Article |
| id | doaj.art-24635ec77265460c93c16096eb303ca4 |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-04-10T07:03:34Z |
| publishDate | 2023-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-24635ec77265460c93c16096eb303ca42023-02-27T10:34:52ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592023-02-011510.1177/17588359231157654Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancerJunyoung ShinBaknoon HamJeong-Han SeoSae Byul LeeIn Ah ParkGyungyub GongSung-Bae KimHee Jin LeeBackground: Despite the introduction of trastuzumab, pathologic complete response (pCR) is not attained in approximately 30–40% of Human epithelial growth factor receptor-2-positive breast cancer. Tumor-infiltrating lymphocytes (TIL) have been suggested as a predictive marker of treatment response, albeit not always effective. We investigated the relationship between trastuzumab, docetaxel, carboplatin, and pertuzumab (TCHP) treatment and immune repertoire as a treatment response predictor. Design: In all, 35 cases were divided into two experimental groups: 10 and 25 cases in the preliminary and main experiments, respectively. In the preliminary experiment, the biopsy tissues before TCHP treatment and the surgical tissues after TCHP treatment were compared. In the main experiment, the biopsy tissues before TCHP treatment were compared according to the TCHP treatment response. Methods: The T-cell repertoire for TRA, TRB, TRG, and TRD, and B-cell repertoire for immunoglobulin heavy, immunoglobulin kappa, and immunoglobulin lambda were evaluated. Whole transcriptome sequencing was also performed. Results: In the preliminary experiment, the density and richness of the T-cell receptor (TCR) and B-cell receptor (BCR) repertoires decreased after treatment, regardless of TCHP response. In the main experiment, the Shannon’s entropy index, density, and length of CDR3 of the TCR and BCR repertoires did not differ significantly in patients who did and did not achieve pCR. The pCR and non-pCR subgroups according to the level of TILs revealed that the non-pCR/lowTIL group had a higher proportion of low-frequency clones than the pCR/lowTIL group in TRA (non-pCR/lowTIL versus pCR/lowTIL, 0.01–0.1%, 63% versus 45.3%; <0.01%, 32.9% versus 51.8%, p < 0.001) and TRB (non-pCR/lowTIL versus pCR/lowTIL, 0.01–0.1%, 26.5% versus 14.7%; <0.01%, 72.0% versus 84.1%, p < 0.001). Conclusions: The role of the diversity, richness, and density of the TCR and BCR repertoires as predictive markers for TCHP response was not identified. Compositions of low-frequency clones could be candidates for predictive factors of TCHP response; however, validation studies and further research are necessary.https://doi.org/10.1177/17588359231157654 |
| spellingShingle | Junyoung Shin Baknoon Ham Jeong-Han Seo Sae Byul Lee In Ah Park Gyungyub Gong Sung-Bae Kim Hee Jin Lee Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancer Therapeutic Advances in Medical Oncology |
| title | Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancer |
| title_full | Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancer |
| title_fullStr | Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancer |
| title_full_unstemmed | Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancer |
| title_short | Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancer |
| title_sort | immune repertoire and responses to neoadjuvant tchp therapy in her2 positive breast cancer |
| url | https://doi.org/10.1177/17588359231157654 |
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