Alterations in immune cell phenotype and cytotoxic capacity in HER2+ breast cancer patients receiving HER2-targeted neo-adjuvant therapy

Gaynor, Nicola; Blanco, Alfonso; Madden, Stephen F.; Moran, Barry; Fletcher, Jean M.; Kaukonen, Damien; Ramírez, Javier Sánchez; Eustace, Alex J.; McDermott, Martina S.J.; Toomey, Sinéad; Teiserskiene, Ausra; Hennessy, Bryan T.; O’Donovan, Norma; Crown, John; Collins, Denis M.

doi:10.1038/s41416-023-02375-y

Cited by 3 publications

(1 citation statement)

References 58 publications

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“…Since PBMC include also T cells with immunosuppressive activity [ 33 ], we have investigated wheter DOX has a preferential effect on a specific T cell population during chemotherapy by analyzing DOX uptake in subsets of CD4 + and CD8 + cells. Despite the CD3 + /CD4 + population is the more represented in PBMC collected from BC patients (Fig.…”

Section: Resultsmentioning

confidence: 99%

Impact of doxorubicin-loaded ferritin nanocages (FerOX) vs. free doxorubicin on T lymphocytes: a translational clinical study on breast cancer patients undergoing neoadjuvant chemotherapy

Sevieri,

Andreata,

Mainini

et al. 2024

J Nanobiotechnol

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Despite the advent of numerous targeted therapies in clinical practice, anthracyclines, including doxorubicin (DOX), continue to play a pivotal role in breast cancer (BC) treatment. DOX directly disrupts DNA replication, demonstrating remarkable efficacy against BC cells. However, its non-specificity toward cancer cells leads to significant side effects, limiting its clinical utility. Interestingly, DOX can also enhance the antitumor immune response by promoting immunogenic cell death in BC cells, thereby facilitating the presentation of tumor antigens to the adaptive immune system. However, the generation of an adaptive immune response involves highly proliferative processes, which may be adversely affected by DOX-induced cytotoxicity. Therefore, understanding the impact of DOX on dividing T cells becomes crucial, to deepen our understanding and potentially devise strategies to shield anti-tumor immunity from DOX-induced toxicity. Our investigation focused on studying DOX uptake and its effects on human lymphocytes. We collected lymphocytes from healthy donors and BC patients undergoing neoadjuvant chemotherapy (NAC). Notably, patient-derived peripheral blood mononuclear cells (PBMC) promptly internalized DOX when incubated in vitro or isolated immediately after NAC. These DOX-treated PBMCs exhibited significant proliferative impairment compared to untreated cells or those isolated before treatment initiation. Intriguingly, among diverse lymphocyte sub-populations, CD8 + T cells exhibited the highest uptake of DOX. To address this concern, we explored a novel DOX formulation encapsulated in ferritin nanocages (FerOX). FerOX specifically targets tumors and effectively eradicates BC both in vitro and in vivo. Remarkably, only T cells treated with FerOX exhibited reduced DOX internalization, potentially minimizing cytotoxic effects on adaptive immunity.Our findings underscore the importance of optimizing DOX delivery to enhance its antitumor efficacy while minimizing adverse effects, highlighting the pivotal role played by FerOX in mitigating DOX-induced toxicity towards T-cells, thereby positioning it as a promising DOX formulation. This study contributes valuable insights to modern cancer therapy and immunomodulation.

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Section: Resultsmentioning

confidence: 99%

Impact of doxorubicin-loaded ferritin nanocages (FerOX) vs. free doxorubicin on T lymphocytes: a translational clinical study on breast cancer patients undergoing neoadjuvant chemotherapy

Sevieri,

Andreata,

Mainini

et al. 2024

J Nanobiotechnol

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Cancer Nanovaccines: Nanomaterials and Clinical Perspectives

Desai,

Chavda,

Singh

et al. 2024

Small

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Cancer nanovaccines represent a promising frontier in cancer immunotherapy, utilizing nanotechnology to augment traditional vaccine efficacy. This review comprehensively examines the current state‐of‐the‐art in cancer nanovaccine development, elucidating innovative strategies and technologies employed in their design. It explores both preclinical and clinical advancements, emphasizing key studies demonstrating their potential to elicit robust anti‐tumor immune responses. The study encompasses various facets, including integrating biomaterial‐based nanocarriers for antigen delivery, adjuvant selection, and the impact of nanoscale properties on vaccine performance. Detailed insights into the complex interplay between the tumor microenvironment and nanovaccine responses are provided, highlighting challenges and opportunities in optimizing therapeutic outcomes. Additionally, the study presents a thorough analysis of ongoing clinical trials, presenting a snapshot of the current clinical landscape. By curating the latest scientific findings and clinical developments, this study aims to serve as a comprehensive resource for researchers and clinicians engaged in advancing cancer immunotherapy. Integrating nanotechnology into vaccine design holds immense promise for revolutionizing cancer treatment paradigms, and this review provides a timely update on the evolving landscape of cancer nanovaccines.

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In-Depth Analysis of the Peripheral Immune Profile of HER2+ Breast Cancer Patients on Neoadjuvant Treatment with Chemotherapy Plus Trastuzumab Plus Pertuzumab

Pesce Viglietti,

Bordignon,

Ostinelli

et al. 2024

IJMS

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Currently, therapy for early-stage human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) is based on the combination of trastuzumab and pertuzumab plus chemotherapy in a neoadjuvant regimen. The INMUNOHER study aimed to detect immunological markers in peripheral blood and their association with treatment response. Sixty-two HER2+ BC patients were recruited. Pre-treatment samples were obtained before the start of treatment, while post-treatment samples were obtained after completing therapy and before surgery and were analyzed by flow cytometry. The pathologic complete response (pCR) rate achieved was 82.3%. The expression of the NKp30, PD-1, and TIM-3 receptors was reduced in the Natural Killer (NK)-CD56dim subset of patients who did not achieve pCR. Following therapy, many changes were found in leukocytes, including alterations in T cell lymphocyte proportions. Also, the percentage of NK cells decreased, and several phenotypic changes were observed in this population. After treatment, IFN-γ production by NK cells against HER2+-cells with or without trastuzumab was significantly reduced. HER2-targeted therapy plus chemotherapy demonstrated high efficacy in most patients, reducing the statistical power for finding immunological markers. However, NK subset phenotypes correlated better with response groups, and numerous changes in the percentage of leukocytes and T and NK cells, as well as changes in the functionality of NK cells, were observed in most patients after treatment, encouraging further research into these immune populations.

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Alterations in immune cell phenotype and cytotoxic capacity in HER2+ breast cancer patients receiving HER2-targeted neo-adjuvant therapy

Cited by 3 publications

References 58 publications

Impact of doxorubicin-loaded ferritin nanocages (FerOX) vs. free doxorubicin on T lymphocytes: a translational clinical study on breast cancer patients undergoing neoadjuvant chemotherapy

Impact of doxorubicin-loaded ferritin nanocages (FerOX) vs. free doxorubicin on T lymphocytes: a translational clinical study on breast cancer patients undergoing neoadjuvant chemotherapy

Cancer Nanovaccines: Nanomaterials and Clinical Perspectives

In-Depth Analysis of the Peripheral Immune Profile of HER2+ Breast Cancer Patients on Neoadjuvant Treatment with Chemotherapy Plus Trastuzumab Plus Pertuzumab

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