Article
Oncology
Zaofeng Yang, Jacquelyne Ka-Li Sun, Marianne M. Lee, Michael K. Chan
Summary: This study validates the effectiveness of p53 restoration in overcoming resistance to immune checkpoint inhibitors (ICIs), and demonstrates that intracellular delivery of p53 protein can be an efficient, safe, and potentially universal strategy to restore p53 activity in tumors carrying TP53 mutation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Dorota Kwapisz
Summary: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and limited treatment options, but it shows higher immunogenicity, tumor-infiltrating lymphocytes (TILs) enrichment, and programmed cell death ligand 1 (PD-L1) expression which make it more suitable for immune checkpoint blockade therapy. Patients with PD-L1-positive TNBC subgroup may benefit the most from immune checkpoint inhibitor (ICI) treatment, and ICI given as first-line treatment in advanced TNBC shows better results than in later lines of treatment. Exciting results have been seen with pembrolizumab in early-stage TNBC, indicating potential approval in (neo)adjuvant settings in the near future.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Immunology
Renhong Huang, Han Wang, Jin Hong, Jiayi Wu, Ou Huang, Jianrong He, Weiguo Chen, Yafen Li, Xiaosong Chen, Kunwei Shen, Zheng Wang
Summary: The study demonstrates that SLC7A5 plays a crucial role in the glutamine metabolic reprogramming of TNBC cells. Inhibition of SLC7A5 significantly suppresses TNBC cell proliferation, migration, and invasion, while increasing immune cell infiltration. Combining SLC7A5 blockade with anti-PD-1 antibody synergistically enhances immune cell infiltration and inhibits tumor progression.
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Medicine, General & Internal
Ryan Sun, Lee-Jen Wei
Summary: This article discusses the clinical benefits of pembrolizumab combined with chemotherapy in patients with triple-negative breast cancer. The authors suggest that both hazard values and ratios should be considered when evaluating clinical benefits.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Oncology
Elie Marcheteau, Thomas Farge, Michael Peres, Guillaume Labrousse, Julie Tenet, Stephanie Delmas, Maud Chusseau, Raphaelle Duprez-Paumier, Camille Franchet, Florence Dalenc, Caroline Imbert, Justine Noujarede, Celine Colacios, Herve Prats, Florence Cabon, Bruno Segui
Summary: TSP1 plays a crucial role in TNBC by influencing TILs content and immunotherapy efficacy, making it a potential therapeutic target in combination with immunotherapy for TNBC treatment.
Review
Health Care Sciences & Services
Tinglin Yang, Wenhui Li, Tao Huang, Jun Zhou
Summary: The advent of immunotherapy, especially immune checkpoint inhibitors (ICIs), has brought drastic changes to antitumor therapy. PD-1 and PD-L1 are promising targets that can encourage the immune system to eliminate cancer cells. Integrating PD-1/PD-L1 inhibitors into existing treatments for early-stage triple-negative breast cancer (TNBC) has attracted attention. This article summarizes the clinical benefit of PD-1/PD-L1 inhibitors in combination with neoadjuvant chemotherapy, adjuvant chemotherapy, and targeted therapy for early-stage TNBC. The potential biomarkers, immune-related adverse events (irAEs), and challenges in TNBC anti-PD-1/PD-L1 therapy are also discussed. Ongoing studies in immunotherapy and the significant clinical prospects of PD-1/PD-L1 inhibitors in early-stage TNBC are highlighted. Further research is necessary to overcome the challenges and maximize the efficacy of anti-PD-1/PD-L1 therapy in TNBC.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Oncology
Zhe Wang, Ruolei Li, Niuniu Hou, Juliang Zhang, Ting Wang, Pengyu Fan, Cheng Ji, Bo Zhang, Liuyin Liu, Yaping Wang, Jing Kong, Qing Yao, Jie Duan, Ge Zhao, Rui Ling, Jian Zhang
Summary: The activation of PRMT5 plays a crucial role in TNBC immunotherapy. PRMT5 selectively methylates KEAP1, leading to the downregulation of NRF2 and its downstream targets, which determine cell fate between pro-ferroptosis and anti-ferroptosis. High levels of PRMT5 protein indicate strong resistance of TNBC to immunotherapy, while PRMT5 inhibitors enhance the therapeutic efficacy of immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Letter
Medicine, General & Internal
Shuvadeep Ganguly, Ajay Gogia
Summary: In the KEYNOTE-522 trial, the addition of Pembrolizumab to neoadjuvant chemotherapy improved pathological complete response rate in early triple-negative breast cancer patients and also improved event-free survival. However, this improvement was predominantly observed in patients who did not achieve a pathological complete response.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Maryam Nakhjavani, Sarah Shigdar
Summary: Triple-negative breast cancer (TNBC) has the worst prognosis among breast cancer subtypes and lacks targeted therapy. Immunotherapy targeting PD-1/PD-L1 has shown promise. Aptamers, with their better tissue penetration and lower production cost compared to mAbs, present a potential pathway for PD-1/PD-L1 modulation in the future.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Oncology
Brie Chun, Joanna Pucilowska, ShuChing Chang, Isaac Kim, Benjamin Nikitin, Yoshinobu Koguchi, William L. Redmond, Brady Bernard, Venkatesh Rajamanickam, Nathan Polaske, Paul A. Fields, Valerie Conrad, Mark Schmidt, Walter J. Urba, Alison K. Conlin, Heather L. McArthur, David B. Page
Summary: This study investigates the effects of pembrolizumab combined with paclitaxel or capecitabine on T-cell subsets in triple-negative breast cancer patients. The results show that these treatments result in similar lymphodepletions across peripheral T-cell subsets and do not alter T-cell clonal diversity. The findings contribute to our understanding of the impact of chemoimmunotherapy on the immune system.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Renato Brito Baleeiro, Peng Liu, Louisa S. Chard Dunmall, Carmela Di Gioia, Ai Nagano, Lauren Cutmore, Jun Wang, Claude Chelala, Lydon Wainaina Nyambura, Peter Walden, Nicholas Lemoine, Yaohe Wang
Summary: This study successfully identified immunogenic neoantigens and generated neoantigen-specific CD8+T cells capable of recognizing human triple-negative breast cancer cells. Using an oncolytic virus as a delivery system, the researchers demonstrated that vaccination with neoantigens can induce a specific CD8+T cell response, slow tumor growth, and increase survival in a mouse model of TNBC. This study provides a promising approach for the development of neoantigen-based immunotherapies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Carolina Mathias, Vanessa Nascimento Kozak, Jessica Maria Magno, Suelen Cristina Soares Baal, Victor Henrique Apolonio dos Santos, Enilze Maria de Souza Fonseca Ribeiro, Daniela Fiori Gradia, Mauro Antonio Alves Castro, Jaqueline Carvalho de Oliveira
Summary: In this article, we review the role of long non-coding RNAs (lncRNAs) in the regulation of the PD-1/PD-L1 pathway and in defining immune-related prognostic signatures in various types of tumors. We also identify two lncRNAs, UCA1 and HCP5, which have not yet been studied in the context of the tumoral immune response in breast cancer, but may have potential as biomarkers for the response to immune checkpoint inhibitors.
Article
Oncology
Carey K. Anders, Mark G. Woodcock, Amanda E. D. Van Swearingen, Dominic T. Moore, Maria J. Sambade, Sonia Laurie, Alexander Robeson, Oleg Kolupaev, Luz A. Cuaboy, Amy L. Garrett, Karen McKinnon, Kristen Cowens, Dante Bortone, Benjamin C. Calhoun, Alec D. Wilkinson, Lisa Carey, Trevor Jolly, Hyman Muss, Katherine Reeder-Hayes, Rebecca Kaltman, Rachel Jankowitz, Vinay Gudena, Oludamilola Olajide, Charles Perou, E. Claire Dees, Benjamin G. Vincent, Jonathan S. Serody
Summary: This study evaluated the efficacy of using a low dose of cyclophosphamide (Cy) to deplete regulatory T cells (T-regs) before initiating pembrolizumab in patients with triple negative breast cancer (TNBC). The results showed that Cy did not significantly decrease T-regs before pembrolizumab and there was a rapid recovery in T-regs after the first cycle of therapy. Baseline samples with increased B cell gene expression were associated with clinical response and immune-related toxicity (IRT).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Pharmacology & Pharmacy
Hualian Zha, Zhanxue Xu, Xichao Xu, Xingyu Lu, Peilin Shi, Youmei Xiao, Hsiang- Tsai, Dandan Su, Fang Cheng, Xiaoli Cheng, Hongbo Chen
Summary: This study developed a cell membrane-derived PD-1 nanovesicle encapsulating low-dose gemcitabine, which synergistically inhibited the proliferation of triple-negative breast cancer cells, improved tumor targeting ability, and increased CD8(+) T cell activation, leading to delayed tumor growth and prolonged survival in mice.
Article
Oncology
Xiaoying Tan, Yan Li, Zhihui Hou, Mingwei Zhang, Li Li, Junmin Wei
Summary: This study aimed to evaluate the anti-tumor efficacy of PD-1 monoclonal antibody with mTOR inhibitor rapamycin or with the anti-diabetic drug metformin in triple negative breast cancer. The combination therapy showed additive effects on suppressing tumor growth and distant metastasis in mice. It also led to increased infiltration of TILs and decreased PD-L1 expression, indicating enhanced antitumor immunity and blockade of PD-1/PD-L1 pathway.
EXPERIMENTAL CELL RESEARCH
(2023)
