Redox Signaling Modulates Activity of Immune Checkpoint Inhibitors in Cancer Patients

Abstract

Although immunotherapy is already a staple of cancer care, many patients may not benefit from these cutting-edge treatments. A crucial field of research now focuses on figuring out how to improve treatment efficacy and assess the resistance mechanisms underlying this uneven response. For a good response, immune-based treatments, in particular immune checkpoint inhibitors, rely on a strong infiltration of T cells into the tumour microenvironment. The severe metabolic environment that immune cells must endure can drastically reduce effector activity. These immune dysregulation-related tumour-mediated perturbations include oxidative stress, which can encourage lipid peroxidation, ER stress, and T regulatory cells dysfunction. In this review, we have made an effort to characterize the status of immunological checkpoints, the degree of oxidative stress, and the part that latter plays in determining the therapeutic impact of immunological check point inhibitors in different neoplastic diseases. In the second section of the review, we will make an effort to assess new therapeutic possibilities that, by affecting redox signalling, may modify the effectiveness of immunological treatment.

The Cellular Stress and Cutaneous Manifestations in Renal Cell Carcinomas—A Narrative Review

“…In RCC, it has been documented that the response to cellular stress interferes with ROS production, angiogenesis, mitochondrial quality, tumor metabolism, inflammation, genetic instability, and the tumor microenvironment (TME) [8,10,[20][21][22]. Low levels of chronic oxidative stress act as a driving force for the malignant transformation of renal epithelial cells [15,23,24].…”

“…Potential pathogenic mechanisms include drug-induced neoantigen formation, unmasking of usually hidden autoantigens, and generalized activation of CD4+ and CD8+ T cells, leading to diffuse keratinocyte apoptosis [121]. Cutaneous immune-related adverse events induced by immune checkpoint inhibitors can be grouped as follows: (a) inflammatory dermatoses (maculopapular eruptions) and papulosquamous disorders (pityriasis rosea, pityriasis lichenoides, pityriasis rubra pilaris, lichenoid and psoriasiform lesions); (b) immune bullous dermatoses (bullous pemphigoid, linear IgA dermatosis); (c) melanocyte alterations (vitiligo-like skin depigmentation, tumoral melanosis and regression of melanocytic nevi, poliosis, and eyebrow or eyelash depigmentation); (d) keratinocyte alterations (benign, precancerous, and cancerous keratinocytic lesions, mainly on photodamaged skin, seborrheic keratoses, actinic keratoses, keratoacanthomas, basal or squamous cell carcinomas); (e) hair abnormalities (non-scarring alopecia, partial or diffuse alopecia areata, hypotrichosis, vi-tiligo, universal alopecia, hair texture changes); (f) nail involvement (nail dystrophy, mostly with psoriasiform or lichenoid features, onychomadesis and proximal onychoschizia, diffuse onycholysis and paronychia); (g) oral involvement (mucositis, gingivitis, xerostomia, dysgeusia, Sjogren syndrome); and (h) rare reactions (photosensitivity, dermatomyositis, panniculitis, granulomatous dermatitis, lymphomatoid or eosinophilic cutaneous toxicity, acute generalized exanthematous pustulosis, neutrophilic dermatoses, toxic epidermal necrolysis) [22,121,[130][131][132].…”

“…Cancer cells alter normal responses to oncogenic stress to redirect them towards supporting growth, even at the expense of organism integrity and homeostasis. The cellular stress response is a translational program of adaptive response activated by oncogenic stress, allowing a cell to survive in the presence of threatening factors, leading to cancer progression [8,[20][21][22].…”

Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention

“…These results may explain the disappointing clinical activity of immune checkpoint inhibitors in the treatment of ovarian cancer [116]. Recently, a link between the expression of CYPs and resistance to immune checkpoint inhibitors in the treatment of cancers was identified [31,117]. It was found that CYP1B1 expression promoted colon cancer cells' resistance to ferroptosis and induced resistance to anti-PD-1 therapy.…”