Review
Biochemistry & Molecular Biology
Hao Zhang, Lin Liu, Jinbo Liu, Pengyuan Dang, Shengyun Hu, Weitang Yuan, Zhenqiang Sun, Yang Liu, Chengzeng Wang
Summary: In recent years, tumor immunotherapy, especially immune checkpoint inhibitors, has shown significant progress. However, these treatments are only effective for a small proportion of patients with solid cancers. Tumor-associated macrophages play a crucial role in the tumor microenvironment and have been shown to impact the therapeutic effect of PD-1/PD-L1 inhibitors.
Review
Immunology
Yunzhou Pu, Qing Ji
Summary: This review summarizes the roles and mechanisms of tumor-associated macrophages (TAMs) in the resistance of PD-1/PD-L1 inhibitors. Various therapies, including inhibition of TAM differentiation and re-education of TAM activation, are available to recover the anticancer efficacy of PD-1/PD-L1 inhibitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiaolei Li, Xiao Su, Rui Liu, Yongsha Pan, Jiankai Fang, Lijuan Cao, Chao Feng, Qianwen Shang, Yongjing Chen, Changshun Shao, Yufang Shi
Summary: Pharmacological modulation of macrophage phenotype by HDAC inhibitors can reshape the tumor immune microenvironment, enhance anti-tumor immune responses, and improve the efficacy of immunotherapies in various tumors.
Article
Biotechnology & Applied Microbiology
Nian Liu, JiangLin Zhang, Mingzhu Yin, Hong Liu, Xu Zhang, Jiaoduan Li, Bei Yan, Yeye Guo, Jianda Zhou, Juan Tao, Shuo Hu, Xiang Chen, Cong Peng
Summary: The study demonstrated that inhibiting xCT may be a promising therapeutic strategy for melanoma, but it also reduces the efficacy of anti-PD-1/PD-L1 treatment by inducing PD-L1 expression and M2 macrophage polarization. Further research is needed to understand the impact of glutamate metabolism on tumor progression and immunotherapy outcomes.
Article
Oncology
Li Wang, John P. Sfakianos, Kristin G. Beaumont, Guray Akturk, Amir Horowitz, Robert P. Sebra, Adam M. Farkas, Sacha Gnjatic, Austin Hake, Sudeh Izadmehr, Peter Wiklund, William K. Oh, Peter M. Szabo, Megan Wind-Rotolo, Keziban Unsal-Kacmaz, Xin Yao, Eric Schadt, Padmanee Sharma, Nina Bhardwaj, Jun Zhu, Matthew D. Galsky
Summary: The study identified dominant molecular and cellular features associated with PD-1/PD-L1 blockade resistance in metastatic urothelial cancer, including an adaptive immune response gene signature linked to response and a protumorigenic inflammation gene signature related to resistance. The balance of adaptive immunity and protumorigenic inflammation in individual tumor microenvironments is associated with PD-1/PD-L1 resistance in urothelial cancer, with a proinflammatory cellular state of myeloid phagocytic cells detectable in tumor and blood samples.
CLINICAL CANCER RESEARCH
(2021)
Review
Immunology
Yiru Long, Xiaolu Yu, Runqiu Chen, Yongliang Tong, Likun Gong
Summary: With programmed death 1/ligand 1 (PD-1/PD-L1) as the cornerstone, anti-PD antibodies have revolutionized immunotherapies for malignancies. However, many patients fail to respond to anti-PD treatment due to resistance or hyperprogression. The study highlights the importance of noncanonical PD-1/PD-L1 expression in various cancers and its impact on the efficacy of anti-PD antibodies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Junjie Liu, Haisu Tao, Tong Yuan, Jiang Li, Jian Li, Huifang Liang, Zhiyong Huang, Erlei Zhang
Summary: Anti-PD-1/PD-L1 therapy is an effective strategy for cancer treatment, but drug resistance is a challenge. Combining this therapy with regorafenib can enhance its efficacy. Regorafenib modifies the tumor microenvironment through various mechanisms and has immunomodulatory effects on immune cells and tumor cells. Studies on the synergistic mechanism of combination therapy can improve cancer treatment and patient selection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xianquan Feng, Zhenzhen Chen, Zhihong Liu, Xiaoling Fu, Hongtao Song, Qian Zhang
Summary: The combination of ATO, PpIX and stabilizer (ATO/PpIX NPs) was self-assembled and targeted to tumors for the first time. This combination induced immunogenic cell death, improved the tumor microenvironment, and enhanced the effectiveness of anti-PD-L1 immunotherapy.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Oncology
Kensuke Kaneko, Chaitanya R. Acharya, Hiroshi Nagata, Xiao Yang, Zachary Conrad Hartman, Amy Hobeika, Philip F. Hughes, Timothy A. J. Haystead, Michael A. Morse, Herbert Kim Lyerly, Takuya Osada
Summary: Combining HS201-PDT with anti-PD-L1 antibody showed enhanced antitumor activity, upregulated CXCR3 gene signature, and improved tumor infiltration by T cells, suggesting the potential of HS201-PDT combined with PD-1/PD-L1 blockade as a treatment strategy for breast cancer. Receptor-ligand interactome analysis revealed enhanced signaling pathways associated with CD8+T cell activation in the combination group.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Jiming Chen, Jie Yang, Wenhui Wang, Danfeng Guo, Chengyan Zhang, Shibo Wang, Xinliang Lu, Xiaofang Huang, Pingli Wang, Gensheng Zhang, Jing Zhang, Jianli Wang, Zhijian Cai
Summary: PD-L1(+) tumor-derived extracellular vesicles (TEVs) cause resistance to anti-PD-L1 antibody therapy by decoying the antibody and being cleared by macrophages, resulting in insufficient blockade of tumor PD-L1.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Cell Biology
Tian Wei, Kangxin Wang, Shuting Liu, Yunxuan Fang, Zixi Hong, Yingfu Liu, Huimin Zhang, Chaoyong Yang, Gaoliang Ouyang, Tiantian Wu
Summary: Periostin, a multifunctional extracellular protein, plays a crucial role in the immune microenvironment of colorectal cancer (CRC) by promoting the infiltration of PD-1+ tumor-associated macrophages (TAMs) and enhancing the expression of PD-1 on TAMs. This, in turn, leads to the production of IL-6 and IFN-g by PD-1+ TAMs, which induce the expression of PD-L1 on colorectal tumor cells. Combined inhibition of periostin and PD-1 shows significant efficacy in suppressing CRC progression.
Review
Oncology
Surbhi Mishra, Sajeen Bahadur Amatya, Sonja Salmi, Vesa Koivukangas, Peeter Karihtala, Justus Reunanen
Summary: Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 have shown promise as contemporary treatments for cancer. This review discusses the potential role of microbiota-derived extracellular vesicles in improving anti-PD-1/PD-L1 therapy outcomes. Bacterial extracellular vesicles have the ability to cross barriers and modify the tumor microenvironment, offering new therapeutic avenues for cancer treatment.
Article
Chemistry, Multidisciplinary
Zhiyong Cai, Jinbo Chen, Zhengzheng Yu, Huihuang Li, Zhi Liu, Dingshan Deng, Jinhui Liu, Chunliang Chen, Chunyu Zhang, Zhenyu Ou, Minfeng Chen, Jiao Hu, Xiongbing Zu
Summary: In order to improve the response rate of immune checkpoint blockade monotherapy (ICB), it is important to identify a potential target for combination therapy. Based on the analysis of tumor microenvironment (TME)-related indicators, it is confirmed that BCAT2 plays a role in shaping a noninflamed TME in bladder cancer. Multiomics analysis reveals that BCAT2 inhibits the recruitment of cytotoxic lymphocytes by suppressing proinflammatory cytokine/chemokine-related pathways and the T-cell-chemotaxis pathway. Immunoassays demonstrate a negative correlation between the secretion of CD8(+)T-cell-related chemokines and BCAT2, resulting in a decrease in the number of CD8(+)T cells around BCAT2(+) tumor cells. The combination of BCAT2 deficiency and anti-PD-1 antibody shows a synergistic effect in vivo, suggesting the potential of BCAT2 in combination therapy. Furthermore, the predictive value of BCAT2 in immunotherapy efficacy is validated in multiple immunotherapy cohorts.
Article
Immunology
Fu-xue Huang, Jun-wan Wu, Xia-qin Cheng, Jiu-hong Wang, Xi-zhi Wen, Jing-jing Li, Qiong Zhang, Hang Jiang, Qiu-yue Ding, Xiao-feng Zhu, Xiao-shi Zhang, Ya Ding, Dan-dan Li
Summary: This study showed that high expression of HHLA2 is associated with better prognosis and improved response to immune checkpoint blockades in melanoma patients. The expression of HHLA2 is also positively correlated with the density of CD8(+) tumor infiltrating lymphocytes.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Jihane Boustani, Benoit Lecoester, Jeremy Baude, Charlene Latour, Olivier Adotevi, Celine Mirjolet, Gilles Truc
Summary: Combining radiation therapy with immune checkpoint inhibitors shows synergistic potential in enhancing anti-tumor immune responses, although optimization of treatment requires consideration of factors such as dose, fractionation, target volume, lymph nodes, and other immunomodulatory agents.
