Exploring genetic and immune underpinnings of the sexual dimorphism in tumor response to immune checkpoints inhibitors: A narrative review

Mazzaschi, Giulia; Quaini, Federico; Buti, Sebastiano

doi:10.1016/j.crphar.2022.100146

Cited by 1 publication

(1 citation statement)

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“…While sex is known to have an effect on the immune response to infections and autoimmune disease, the impact of sex on response to immunotherapy remains unclear, with conflicting results seen in meta-analyses of multiple solid tumours [35]. While there have been significant attempts to explore molecular profiles to better understand the effects of sex on immunotherapy efficacy, ultimately, how sex affects one's tumour microenvironment and response to immunotherapy remains largely unknown and warrants further exploration [36,37].…”

Section: Discussionmentioning

confidence: 99%

Sex as a Predictor of Response to Immunotherapy in Advanced Cutaneous Squamous Cell Carcinoma

Yeo,

Genenger,

Aghmesheh

et al. 2023

Cancers

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Approximately 3–5% of patients with cutaneous squamous cell carcinoma (CSCC) develop advanced disease, accounting for roughly 1% of all cancer deaths in Australia. Immunotherapy has demonstrated significant clinical benefit in advanced CSCC in several key phase II studies; however, there are limited data for patients treated outside of clinical trials. This is particularly relevant in advanced CSCC, which is most often seen in elderly patients with significant comorbidities. Thus, we aim to describe our experience with immunotherapy in a cohort of patients with advanced CSCC in Australia. We retrospectively reviewed all advanced CSCC patients treated with immunotherapy within the Illawarra and Shoalhaven Local Health District. Among the 51 patients treated with immunotherapy, there was an objective response rate (ORR) of 53% and disease control rate (DCR) of 67%. Our most significant predictor of response was sex, with male patients more likely to have better responses compared to female patients (DCR 85% vs. 41%, p < 0.0001), as well as improved progression-free survival (HR 4.6, 95%CI 1.9–10.8, p = 0.0007) and overall survival (HR 3.0, 95%CI 1.3–7.1, p = 0.006). Differential expression analysis of 770 immune-related genes demonstrated an impaired CD8 T-cell response in female patients. Our observed ORR of 53% is similar to that described in current literature with durable responses seen in the majority of patients.

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Section: Discussionmentioning

confidence: 99%