Toxicities associated with checkpoint inhibitors—an overview

Spiers, Laura; Coupe, Nicholas; Payne, Miranda

doi:10.1093/rheumatology/kez418

Cited by 91 publications

(74 citation statements)

References 67 publications

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“…Taking the above into account, the linical testing of PD-1-blocking antibodies in MPN seems highly relevant given the fact that the JAK2 V617F mutation enhances the expression of PD-L1 on transformed cells [ 69 ]. Taking the increased risk of autoimmune disease in patients with MPN into account, one needs to carefully consider the use of PD-1-blocking antibodies, as treatment with these frequently results in the emergence of autoimmune phenomena [ 125 ]. To date, only one study is evaluating the clinical efficacy of immune checkpoint inhibitors in patients with MPN (NCT03065400), but no clinical results have been reported at the time of the writing of this paper.…”

Section: Potential Cancer Immune Therapeutic Strategies For Mpnmentioning

confidence: 99%

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms

Holmström

Hasselbalch

Andersen

2020

Cancers

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Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPN) are neoplastic diseases of the hematopoietic stem cells in the bone marrow. MPN are characterized by chronic inflammation and immune dysregulation. Of interest, the potent immunostimulatory cytokine interferon-α has been used to treat MPN for decades. A deeper understanding of the anti-cancer immune response and of the different immune regulatory mechanisms in patients with MPN has paved the way for an increased perception of the potential of cancer immunotherapy in MPN. Therapeutic vaccination targeting the driver mutations in MPN is one recently described potential new treatment modality. Furthermore, T cells can directly react against regulatory immune cells because they recognize proteins like arginase and programmed death ligand 1 (PD-L1). Therapeutic vaccination with arginase or PD-L1 therefore offers a novel way to directly affect immune inhibitory pathways, potentially altering tolerance to tumor antigens like mutant CALR and mutant JAK2. Other therapeutic options that could be used in concert with therapeutic cancer vaccines are immune checkpoint–blocking antibodies and interferon-α. For more advanced MPN, adoptive cellular therapy is a potential option that needs more preclinical investigation. In this review, we summarize current knowledge about the immune system in MPN and discuss the many opportunities for anti-cancer immunotherapy in patients with MPN.

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Section: Potential Cancer Immune Therapeutic Strategies For Mpnmentioning

confidence: 99%

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms

Holmström

Hasselbalch

Andersen

2020

Cancers

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“…Recently, immune checkpoint inhibitors have been widely used for advanced cancers. Among these agents, nivolumab is one of the earliest to be developed and is used to treat various cancers, including renal cell carcinoma, malignant melanoma, and Hodgkin lymphoma [1].…”

Section: Introductionmentioning

confidence: 99%

“…The hyperreflective band became wider and more prominent even in the regions without retinal detachment (c, d: yellow arrows). The choroidal thickness reached 341 μm in the right eye and 370 μm in the left eye subclasses of immune checkpoint inhibitors are each associated with several characteristic immunity-related complications [1]. Among ocular complications, dry eye (< 1-5%), uveitis-like symptoms (< 1%), and Vogt-Koyanagi-Harada (VKH) disease (incidence unknown) have been reported [2].…”

Section: Introductionmentioning

confidence: 99%

Bilateral multiple serous retinal detachments after treatment with nivolumab: a case report

et al. 2020

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Background: Immune checkpoint inhibitors have recently been widely used for advanced cancers and are known to cause ocular complications. We herein report a case developing bilateral serous retinal detachments, without ocular inflammation, after starting nivolumab treatment. Case presentation: A 73-year-old man was referred to our hospital, having become aware of metamorphopsia 2 months after starting nivolumab (anti-programmed cell death protein 1 monoclonal antibody) for malignant melanoma of the nasal cavity. The initial corrected visual acuity of the right eye was 20/20, and that of the left eye was 20/16. There were no inflammatory findings in the anterior segment or the vitreous. Vitelliform lesions were found in the macular area of both ocular fundi, consistent with serous retinal detachment and subretinal deposits. Swept source optical coherence tomography showed diffuse thickening of the outer photoreceptor segment and thickening of the choroid. Two months after the initial diagnosis, multiple vitelliform lesions were noted, and the fundus findings had worsened. Indocyanine green fluorescein angiography showed delayed inflow in the peripapillary and posterior pole regions in the early phase of imaging. Fundus autofluorescence showed hyperautofluorescence consistent with most of the vitelliform lesions on color fundus photography. Conclusions: Nivolumab may have impaired the pumping and phagocytosis functions of retinal pigment epithelial cells, resulting in bilateral serous retinal detachments and thickening of the photoreceptor outer segment. This is the first case report, to our knowledge, describing multiple bilateral serous retinal detachments and outer segment thickening without inflammation in a patient treated with nivolumab.

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“… 5 Those combinations appeared to enhance tumor suppression compared with single antibody administration, but side effects were more frequent and in some cases more serious. 36 , 37 There may be limitations to accelerating CTL function by direct control of switches on T cells. Considering how cancers escape from immune surveillance, cancer cells modulate the TME to induce immune tolerance to themselves in the host immune system.…”

Section: Discussionmentioning

confidence: 99%

CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy

Pan

Nishikawa

Chang

et al. 2021

Molecular Therapy - Oncolytics

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Breast cancer has a high risk of metastasis; however, no effective treatment has been established. We developed a novel immunotherapy for breast cancer to enhance cytotoxic T lymphocytes against cancer cells using N1-type neutrophils with anti-tumor properties. For this purpose, we combined CXCL2 (CXC chemokine ligand 2) plasmid DNA with inactivated Sendai virus (hemagglutinating virus of Japan)-envelope (HVJ-E). The combination of CXCL2 DNA and HVJ-E (C/H) suppressed the growth of murine breast cancers in orthotopic syngeneic models by enhancing cytotoxic T lymphocytes and inhibited lung metastasis of breast cancer from primary lesions. N1-type neutrophils (CD11b + Ly6G + FAS + ) increased in the tumor microenvironment with C/H treatment, and tumor suppression and cytotoxic T lymphocyte activation from C/H was blocked after administrating anti-neutrophil antibodies, which indicates the role of N1-type neutrophils in cancer immunotherapy. We also demonstrated that the anti-tumor activities of C/H treatment were enhanced by the administration of anti-PD-1 antibodies through neutrophil-mediated cytotoxic T lymphocyte activation. Thus, the triple combination of C/H and anti-PD-1 antibody C/H treatment may provide an improvement in cancer immunotherapy.

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Toxicities associated with checkpoint inhibitors—an overview

Cited by 91 publications

References 67 publications

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms

Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms

Bilateral multiple serous retinal detachments after treatment with nivolumab: a case report

CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy

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