Mechanisms of Resistance and Strategies to Combat Resistance in PD-(L)1 Blockade

Moise, John; Murthy, Jeevan; Dabir, Dolma; Yu, Stephen; Kisto, Farah; Herron, Emily; Aulakh, Sonikpreet

doi:10.3390/immuno2040041

Cited by 2 publications

(2 citation statements)

References 163 publications

(196 reference statements)

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“…The consequences consist of the impairment of PD-1 signaling and the activity of T lymphocytes. The overexpression of TIM-3 in regulatory T lymphocytes causes the dysfunction of tumor-infiltrative lymphocytes, leading to resistance to treatment [175,176]. Cells refractory to treatment have undergone mutations, losing their response to 7-interferon or MHC class I [177].…”

Section: Treatment Of Cutaneous Melanomamentioning

confidence: 99%

A Narrative Review of Current Knowledge on Cutaneous Melanoma

Caraban,

Aschie,

Deacu

et al. 2024

Clinics and Practice

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Cutaneous melanoma is a public health problem. Efforts to reduce its incidence have failed, as it continues to increase. In recent years, many risk factors have been identified. Numerous diagnostic systems exist that greatly assist in early clinical diagnosis. The histopathological aspect illustrates the grim nature of these cancers. Currently, pathogenic pathways and the tumor microclimate are key to the development of therapeutic methods. Revolutionary therapies like targeted therapy and immune checkpoint inhibitors are starting to replace traditional therapeutic methods. Targeted therapy aims at a specific molecule in the pathogenic chain to block it, stopping cell growth and dissemination. The main function of immune checkpoint inhibitors is to boost cellular immunity in order to combat cancer cells. Unfortunately, these therapies have different rates of effectiveness and side effects, and cannot be applied to all patients. These shortcomings are the basis of increased incidence and mortality rates. This study covers all stages of the evolutionary sequence of melanoma. With all these data in front of us, we see the need for new research efforts directed at therapies that will bring greater benefits in terms of patient survival and prognosis, with fewer adverse effects.

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Section: Treatment Of Cutaneous Melanomamentioning

confidence: 99%

A Narrative Review of Current Knowledge on Cutaneous Melanoma

Caraban,

Aschie,

Deacu

et al. 2024

Clinics and Practice

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“…Nevertheless, the clinical achievements observed with PD-1/PD-L1 immune checkpoint therapy are not as expected, as patient responses to the treatment exhibit a degree of heterogeneity and unpredictability. The response to immune checkpoint inhibitors targeting PD-1/PD-L1 is influenced by complex genetic and epigenetic interactions between immune cells and tumor cells [61]. Additional, patient-specific factors, such as age and the presence of comorbidities, could influence their response to immunotherapy [40,62].…”

Section: Overview Of the Clinical Significance Of Pd-l1 In Cancermentioning

confidence: 99%

Autophagy as a Target for Non-Immune Intrinsic Functions of Programmed Cell Death-Ligand 1 in Cancer

García-Pérez,

Pérez-Torres,

Baltierra-Uribe

et al. 2023

IJMS

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Autophagy is a catabolic process that is essential to the maintenance of homeostasis through the cellular recycling of damaged organelles or misfolded proteins, which sustains energy balance. Additionally, autophagy plays a dual role in modulating the development and progression of cancer and inducing a survival strategy in tumoral cells. Programmed cell death-ligand 1 (PD-L1) modulates the immune response and is responsible for maintaining self-tolerance. Because tumor cells exploit the PD-L1–PD-1 interaction to subvert the immune response, immunotherapy has been developed based on the use of PD-L1-blocking antibodies. Recent evidence has suggested a bidirectional regulation between autophagy and PD-L1 molecule expression in tumor cells. Moreover, the research into the intrinsic properties of PD-L1 has highlighted new functions that are advantageous to tumor cells. The relationship between autophagy and PD-L1 is complex and still not fully understood; its effects can be context-dependent and might differ between tumoral cells. This review refines our understanding of the non-immune intrinsic functions of PD-L1 and its potential influence on autophagy, how these could allow the survival of tumor cells, and what this means for the efficacy of anti-PD-L1 therapeutic strategies.

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Mechanisms of Resistance and Strategies to Combat Resistance in PD-(L)1 Blockade

Cited by 2 publications

References 163 publications

A Narrative Review of Current Knowledge on Cutaneous Melanoma

A Narrative Review of Current Knowledge on Cutaneous Melanoma

Autophagy as a Target for Non-Immune Intrinsic Functions of Programmed Cell Death-Ligand 1 in Cancer

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