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Cancers
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Breast Cancer: Immune Response, Immune Microenvironment, and Immunotherapy
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Breast Cancer: Immune Response, Immune Microenvironment, and Immunotherapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 15 September 2026 | Viewed by 1600

Special Issue Editors

Dr. Ravindra Deshpande

E-Mail
Guest Editor
Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC, USA
Interests: breast cancer; immunotherapy resistance; checkpoint blockade; immune cells
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ann Richmond

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Guest Editor
Vanderbilt University Medical Center, 432-B Preston Building, Nashville, TN 37232-6840, USA
Interests: cancer; breast cancer; antitumor immunity; cancer immunity; immune checkpoint inhibitor

Special Issue Information

Dear Colleagues,

Breast cancer remains a leading cause of cancer-related mortality, with growing research emphasizing its complex interaction with the immune system. The immune response and tumor immune microenvironment (TIME) significantly influence disease progression and therapeutic outcomes. Immunotherapy approaches, including immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapy, have shown promise, though resistance remains a major challenge. This resistance stems from both intrinsic mechanisms (genetic mutations, tumor heterogeneity, antigen loss) and extrinsic factors (immunosuppressive microenvironment, dysfunctional immune cell infiltration).

This Special Issue will explore the diverse mechanisms of resistance in breast cancer immunotherapy, with a particular focus on the pivotal role of patient stratification based on immune profiles. By categorizing patients according to distinct immunological characteristics, this Special Issue will deepen our understanding of how these classifications influence therapeutic outcomes. Furthermore, it will synthesize current evidence linking immune-based patient subgroups to differential treatment responses, ultimately advocating for biomarker-driven strategies that enhance the precision and effectiveness of personalized immunotherapy in breast cancer.

Dr. Ravindra Deshpande
Prof. Dr. Ann Richmond
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • breast cancer
  • immune response
  • tumor immune microenvironment
  • immunotherapy resistance
  • intrinsic and extrinsic mechanisms
  • immune checkpoint inhibitors
  • T-cell dysfunction
  • cytokines
  • cancer vaccines
  • tumor immunosuppression

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Published Papers (2 papers)

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Research

14 pages, 5973 KB  
Article
Hyperthermia Combined with Anti-CTLA-4 Antibody Induces Tumor Microenvironment Remodeling Involving CD4+ T Cells in Local and Distant Antitumor Effects in a Murine Triple-Negative Breast Cancer
by Ayaka Okuuchi, Yoriko Ibuki, Shohei Katsuki, Kazumasa Minami, Shotaro Tatekawa, Keisuke Tamari, Wataru Takenaka, Masahiko Koizumi, Kazuhiko Ogawa and Yutaka Takahashi
Cancers 2026, 18(8), 1295; https://doi.org/10.3390/cancers18081295 - 20 Apr 2026
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Abstract
Background/Objectives: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Our previous study demonstrated that combination therapy with local hyperthermia (HT) and anti-CTLA-4 antibody (C4), an immune checkpoint inhibitor, induced regression of both local and distant tumors. However, tumor [...] Read more.
Background/Objectives: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Our previous study demonstrated that combination therapy with local hyperthermia (HT) and anti-CTLA-4 antibody (C4), an immune checkpoint inhibitor, induced regression of both local and distant tumors. However, tumor microenvironment (TME) changes in local and distant tumors following local HT and C4 remain unclear. Here, we aimed to evaluate TME changes in local and distant tumors induced by local HT + C4 therapy. Methods: Murine TNBC cells were inoculated in both legs of male BALB/cAJcl mice, and only one leg was treated with HT (42.5 °C for 20 min). C4 was administered intraperitoneally every 3 days for a total of 3 doses. For CD4+ T cell depletion experiments, anti-CD4 antibody (αCD4) was administered intraperitoneally every 3 days for a total of 12 doses. Tumor-infiltrating immune cells in locally heated tumors and unheated distant tumors were analyzed 9 days after the initial treatment. Furthermore, tumor growth in heated tumors and unheated distant tumors under αCD4 administration was evaluated. Results: HT + C4 therapy increased the proportion of helper T cells and elevated the ratio of cytotoxic T cells plus helper T cells to myeloid-derived suppressor cells in both heated tumors and unheated distant tumors. The HT + C4 + αCD4 group exhibited significantly larger tumor growth, compared with the HT + C4 group in both heated (p < 0.01) and unheated distant tumors (p < 0.01). Conclusions: These results suggest that combination therapy of HT and C4 favorably modulates the TME. CD4+ T cell infiltration may contribute to both local and distant antitumor effects. Full article
(This article belongs to the Special Issue Breast Cancer: Immune Response, Immune Microenvironment, and Immunotherapy)
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13 pages, 622 KB  
Article
Immune-Related Adverse Events in Breast Cancer Patients Who Received Neoadjuvant Chemotherapy with Pembrolizumab: What Needs to Be Managed Before Surgery
by Jeeyeon Lee, Byeongju Kang, Joon Suk Moon, Taegyu Um, Jung Eun Choi, Moohyun Lee, Yee Soo Chae, Soo Jung Lee, In Hee Lee, Soo Jung Lee, Su Hwan Kang, Sung Ae Koh, Sun Hee Kang, Keon Uk Park, Hyera Kim and Ho Yong Park
Cancers 2026, 18(6), 919; https://doi.org/10.3390/cancers18060919 - 12 Mar 2026
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Abstract
Background: Pembrolizumab is a novel immunotherapy agent that improves oncological outcomes for various cancers. This study aimed to investigate immune-related adverse events (irAEs) that occurred after neoadjuvant chemotherapy (NAC) with pembrolizumab for triple-negative breast cancer (TNBC) and to identify fatal irAEs that should [...] Read more.
Background: Pembrolizumab is a novel immunotherapy agent that improves oncological outcomes for various cancers. This study aimed to investigate immune-related adverse events (irAEs) that occurred after neoadjuvant chemotherapy (NAC) with pembrolizumab for triple-negative breast cancer (TNBC) and to identify fatal irAEs that should be addressed before surgery under general anesthesia. Methods: A total of 82 patients who received NAC with pembrolizumab followed by surgery were reviewed based on their medical records. All irAEs during NAC were evaluated and classified into nine categories: systemic, dermatologic, central nervous, musculoskeletal, endocrine, gastrointestinal, respiratory, ocular, and hematologic systems. Clinicopathologic characteristics were compared between patients with and without irAEs, and cases in which surgery was postponed due to irAEs were reviewed and analyzed. Results: Fifty-nine patients (72.0%) experienced irAEs after NAC with pembrolizumab. The mean NAC period was 140.3 days, with a 39.8-day window to surgery. The most common and second most common irAEs were myalgia (n = 33, 40.3%) and skin rash/dermatitis (n = 31, 37.8%), respectively. There were 1 case (1.2%) of adrenal insufficiency and 16 cases (19.5%) of thyroid dysfunction as irAEs. In 6 cases (7.3%), surgery was postponed due to irAEs [systemic (n = 2, 33.3%); endocrine (n = 3, 50.0%); increased transaminase (n = 1, 16.7%)], with a mean delay of 64.5 days (range, 57–80 days). Conclusions: IrAEs following NAC with pembrolizumab in TNBC were diverse and included those severe enough to affect the timing of surgery under general anesthesia. These irAEs should be monitored continuously during NAC and detected early to address them when they occur. Full article
(This article belongs to the Special Issue Breast Cancer: Immune Response, Immune Microenvironment, and Immunotherapy)
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