Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation

Wu, M. K.; Huang, Qianrui; Xie, Yao; Wu, Xuyi; Ma, Huili; Zhang, Yiwen; Xia, Yong

doi:10.1186/s13045-022-01242-2

Cited by 239 publications

(166 citation statements)

References 317 publications

(352 reference statements)

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“…ICI combination strategies with curative potential have been focused on in the field of cancer therapy. Antiangiogenesis agents, cytotoxic chemotherapeutic drugs, and radiotherapy are the most commonly used combination therapies ( 24 ). The disseminated disease in the patient required chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary

et al. 2022

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BackgroundCancer of unknown primary (CUP) is heterogeneous and has a wide variety of clinical presentations and a poor prognosis in most patients, with a median overall survival of only 6 months. The development of molecular profiling contributes to precision therapy, and targeted drugs and immune checkpoint inhibitors (ICIs) greatly promote individualized treatment.Case presentationHere, we reported a case of an unfavorable subset of CUP who had a long time of survival after the immunotherapy-prominent comprehensive treatment. A 48-year-old man presented with back pain and a cough. A diagnostic work-up showed bone marrow, multiple bones, and lymph node metastasis. Lymph node pathology implies metastatic poorly differentiated cancer. Next-generation sequencing (NGS) showed no special targets, but the tumor proportion score (TPS) of programmed death-ligand 1 (PD-L1) was 80% and the tumor mutation burden (TMB) was 16.7 per million bases. After two cycles of pembrolizumab 200 mg D1 plus nanoparticle albumin-bound (nab)-paclitaxel 200 mg D1&8 (q3w), PET-CT and bone marrow aspiration cytology showed a complete response (CR). Subsequently, pembrolizumab alone was used for three months. The left inguinal lymph nodes showed new metastasis. After two cycles of the combination treatment of pembrolizumab and (nab)-paclitaxel, a partial response (PR) was achieved. After seven months, retroperitoneal lymph nodes showed new metastasis, and the sequential treatment with radiotherapy and pembrolizumab exhibited encouraging efficacy. To date, the patient has survived nearly 40 months with the combination therapy.ConclusionsThe ICI-prominent comprehensive treatment provided clinical benefit for the reported case of CUP. Thus, CUP patients with markers of benefiting from immunotherapy should be actively treated with immunotherapy to improve their prognosis.

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Section: Discussionmentioning

confidence: 99%

Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary

et al. 2022

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“…The combination of PD-L1 and PD-1 results in the loss of the killing ability of tumor-infiltrating lymphocytes, which leads to uninhibited tumor growth. Therefore, the destruction of the interaction between PD-L1 and PD-1 manifests tremendous potential in releasing the lethality of the immune system to cancer cells [ 128 , 129 ]. Here, we summarize the research progress of small-molecule agents that target the PD-L1/PD-1 axis and PD-L1 inhibitors (Table 3 ).…”

Section: Targeting Pd-l1 and The Pd-l1 Regulatory Pathway For Cancer ...mentioning

confidence: 99%

Current insight into the regulation of PD-L1 in cancer

Liu

et al. 2022

Exp Hematol Oncol

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The molecular mechanisms underlying cancer immune escape are a core topic in cancer immunology research. Cancer cells can escape T cell-mediated cellular cytotoxicity by exploiting the inhibitory programmed cell-death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1, CD274) immune checkpoint. Studying the PD-L1 regulatory pattern of tumor cells will help elucidate the molecular mechanisms of tumor immune evasion and improve cancer treatment. Recent studies have found that tumor cells regulate PD-L1 at the transcriptional, post-transcriptional, and post-translational levels and influence the anti-tumor immune response by regulating PD-L1. In this review, we focus on the regulation of PD-L1 in cancer cells and summarize the underlying mechanisms.

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“…In addition, CD28 has also been demonstrated to confer a primary target for PD-1, indicating a common pathway with CTLA4. The PD-1—PD-L1 interaction attenuates T lymphocyte immune response, and in the setting of cancer, is a major contributor to impaired anti-cancer immune response [ 25 ].…”

Section: Oncologic Immunomodulationmentioning

confidence: 99%

Virus-Based Immuno-Oncology Models

2022

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Immunotherapy has been extensively explored in recent years with encouraging results in selected types of cancer. Such success aroused interest in the expansion of such indications, requiring a deep understanding of the complex role of the immune system in carcinogenesis. The definition of hot vs. cold tumors and the role of the tumor microenvironment enlightened the once obscure understanding of low response rates of solid tumors to immune check point inhibitors. Although the major scope found in the literature focuses on the T cell modulation, the innate immune system is also a promising oncolytic tool. The unveiling of the tumor immunosuppressive pathways, lead to the development of combined targeted therapies in an attempt to increase immune infiltration capability. Oncolytic viruses have been explored in different scenarios, in combination with various chemotherapeutic drugs and, more recently, with immune check point inhibitors. Moreover, oncolytic viruses may be engineered to express tumor specific pro-inflammatory cytokines, antibodies, and antigens to enhance immunologic response or block immunosuppressive mechanisms. Development of preclinical models capable to replicate the human immunologic response is one of the major challenges faced by these studies. A thorough understanding of immunotherapy and oncolytic viruses’ mechanics is paramount to develop reliable preclinical models with higher chances of successful clinical therapy application. Thus, in this article, we review current concepts in cancer immunotherapy including the inherent and synthetic mechanisms of immunologic enhancement utilizing oncolytic viruses, immune targeting, and available preclinical animal models, their advantages, and limitations.

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Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation

Cited by 239 publications

References 317 publications

Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary

Case Report: Successful Immunotherapy Improved the Prognosis of the Unfavorable Subset of Cancer of Unknown Primary

Current insight into the regulation of PD-L1 in cancer

Virus-Based Immuno-Oncology Models

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