Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1?

Singh, Puneet; Souza, Paul de; Scott, K. John; Hall, Bruce M.; Verma, Nirupama D.; Becker, Therese M.; Toh, James Wei Tatt; Sajinovic, Mila; Spring, Kevin

doi:10.1186/s41231-019-0032-9

Cited by 6 publications

(2 citation statements)

References 112 publications

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“…The advent of clinical trials with ICIs in veterinary medicine intensified in this decade, preceded by the growth of research in people and approval of the first ICIs since 2011: ipilimumab (anti-CTLA-4), pembrolizumab (anti-PD-1), and nivolumab (anti-PD-1) [ 77 , 78 ]. Therapies targeting the PD-1/PDL-1 and CTLA-4 checkpoints were pioneers in human medicine, and a few studies have investigated a similar therapeutic approach in canine tumours [ 6 , 77 , 79 , 80 ].…”

Section: The Expression and Clinical Relevance Of Immune Checkpoints ...mentioning

confidence: 99%

Checkpoint Inhibitors in Dogs: Are We There Yet?

Giuliano,

Pimentel,

Horta

2024

Cancers

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Immune checkpoint inhibitors (ICI) have revolutionised cancer treatment in people. Immune checkpoints are important regulators of the body’s reaction to immunological stimuli. The most studied immune checkpoint molecules are programmed death (PD-1) with its ligand (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) with its ligands CD80 (B7-1) and CD86 (B7-2). Certain tumours can evade immunosurveillance by activating these immunological checkpoint targets. These proteins are often upregulated in cancer cells and tumour-infiltrating lymphocytes, allowing cancer cells to evade immune surveillance and promote tumour growth. By blocking inhibitory checkpoints, ICI can help restore the immune system to effectively fight cancer. Several studies have investigated the expression of these and other immune checkpoints in human cancers and have shown their potential as therapeutic targets. In recent years, there has been growing interest in studying the expression of immune checkpoints in dogs with cancer, and a few small clinical trials with ICI have already been performed on these species. Emerging studies in veterinary oncology are centred around developing and validating canine-targeted antibodies. Among ICIs, anti-PD-1 and anti-PD-L1 treatments stand out as the most promising, mirroring the success in human medicine over the past decade. Nevertheless, the efficacy of caninized antibodies remains suboptimal, especially for canine oral melanoma. To enhance the utilisation of ICIs, the identification of predictive biomarkers for treatment response and the thorough screening of individual tumours are crucial. Such endeavours hold promise for advancing personalised medicine within veterinary practice, thereby improving treatment outcomes. This article aims to review the current research literature about the expression of immune checkpoints in canine cancer and the current results of ICI treatment in dogs.

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Section: The Expression and Clinical Relevance Of Immune Checkpoints ...mentioning

confidence: 99%

Checkpoint Inhibitors in Dogs: Are We There Yet?

Giuliano,

Pimentel,

Horta

2024

Cancers

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“…Currently, absolute pre-treatment lymphocyte counts, ratios of different immune cell populations (e.g. Teff/Treg), or proportions of NK cells, CD4 + T and CD8 + T cells, Tregs, and MDSCs appear to be the most promising candidates [1].…”

Section: Introductionmentioning

confidence: 99%

Peripheral blood biomarkers in immune checkpoint inhibition therapy in metastatic melanoma.

Ghelani,

Mandava,

Bou Zerdan

et al. 2024

JCO

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e21543 Background: Immune checkpoint inhibitors are extensively employed in the management of various solid cancers. Our study aims to assess the potential prognostic and predictive value of peripheral blood biomarkers, as well as their correlation with adverse events. Methods: In this study, we conducted a retrospective analysis of data retrieved from a cohort of 23 patients diagnosed with metastatic melanoma at a single institution between 2015 and 2019. Specifically, we focused on analyzing the neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil+monocyte-to-absolute lymphocyte+eosinophil ratio (ANMC/ALEC) from complete blood count (CBC), and lactate dehydrogenase (LDH) level from peripheral blood to assess their correlation with progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs). Results: Our findings revealed that NLR values less than 0.34 and ANMC/ALEC ratio less than 3.45 were associated with improved PFS and OS, as well as a lower incidence of immune-related adverse events, which supports our initial hypothesis. However, these results were not statistically significant due to the low power of our study. On the other hand, high NLR values were significantly associated with higher pre-treatment LDH levels (P-value = 0.037), which is a well-established adverse prognostic factor in melanoma. Additionally, high ANMC/ALEC ratios were also found to be associated with high LDH levels, although this relationship was not statistically significant (P-value = 0.133). Conclusions: The results of our study suggest that patients with lower pre-treatment NLR and ANMC/ALEC ratios have better PFS and OS, as well as lower incidence of irAEs. Conversely, those with high NLR and high ANMC/ALEC ratios exhibited lower PFS and OS, as well as higher incidence of irAEs. High NLR and ANMC/ALEC ratios were also found to be associated with higher pre-treatment LDH levels, which have previously been demonstrated to be an adverse prognostic factor in melanoma. [Table: see text]

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Targeted Therapies in Cancer Treatment

Cavalcanti

Soares

2021

Advances in Cancer Treatment

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Biomarkers in immune checkpoint inhibition therapy for cancer patients: what is the role of lymphocyte subsets and PD1/PD-L1?

Cited by 6 publications

References 112 publications

Checkpoint Inhibitors in Dogs: Are We There Yet?

Checkpoint Inhibitors in Dogs: Are We There Yet?

Peripheral blood biomarkers in immune checkpoint inhibition therapy in metastatic melanoma.

Targeted Therapies in Cancer Treatment

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