Sex-Related Differences in the Immune System Drive Differential Responses to Anti-PD-1 Immunotherapy

Immune checkpoint inhibitors, such as anti-PD-1 antibodies, represent a significant advancement in cancer immunotherapy, but their efficacy varies notably between individuals, influenced by complex biological systems. Recent evidence suggests that sex-related biological differences play a pivotal ro...

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Main Authors: Sonja Cotra, Mohammad Kohandel, Michelle Przedborski
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/14/12/1513
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author Sonja Cotra
Mohammad Kohandel
Michelle Przedborski
author_facet Sonja Cotra
Mohammad Kohandel
Michelle Przedborski
author_sort Sonja Cotra
collection DOAJ
description Immune checkpoint inhibitors, such as anti-PD-1 antibodies, represent a significant advancement in cancer immunotherapy, but their efficacy varies notably between individuals, influenced by complex biological systems. Recent evidence suggests that sex-related biological differences play a pivotal role in modulating these responses. This study uses a systems biology approach to examine how sex-specific differences in the immune system contribute to variability in the response to treatment. Our model extends previous frameworks by incorporating sex-specific parameters that reflect observed immunological distinctions. The results from the simulation studies align with our clinical observations, showing that on average, males exhibit a more robust response to anti-PD-1 treatment compared to females. Additionally, this study explores the potential of combination therapy with recombinant IL-12, revealing sex-specific differences in treatment efficacy. These findings underscore the need for personalized immunotherapy strategies that consider individual immunological profiles, including sex, to optimize treatment outcomes.
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spelling doaj-art-4a2dfb3045a1472592661fb5fa7725f22025-08-20T02:00:56ZengMDPI AGBiomolecules2218-273X2024-11-011412151310.3390/biom14121513Sex-Related Differences in the Immune System Drive Differential Responses to Anti-PD-1 ImmunotherapySonja Cotra0Mohammad Kohandel1Michelle Przedborski2Department of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, CanadaDepartment of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, CanadaDepartment of Applied Mathematics, University of Waterloo, Waterloo, ON N2L 3G1, CanadaImmune checkpoint inhibitors, such as anti-PD-1 antibodies, represent a significant advancement in cancer immunotherapy, but their efficacy varies notably between individuals, influenced by complex biological systems. Recent evidence suggests that sex-related biological differences play a pivotal role in modulating these responses. This study uses a systems biology approach to examine how sex-specific differences in the immune system contribute to variability in the response to treatment. Our model extends previous frameworks by incorporating sex-specific parameters that reflect observed immunological distinctions. The results from the simulation studies align with our clinical observations, showing that on average, males exhibit a more robust response to anti-PD-1 treatment compared to females. Additionally, this study explores the potential of combination therapy with recombinant IL-12, revealing sex-specific differences in treatment efficacy. These findings underscore the need for personalized immunotherapy strategies that consider individual immunological profiles, including sex, to optimize treatment outcomes.https://www.mdpi.com/2218-273X/14/12/1513systems biologyimmune checkpoint inhibitorssex-specific differencespersonalized immunotherapyanti-PD-1 immunotherapy
spellingShingle Sonja Cotra
Mohammad Kohandel
Michelle Przedborski
Sex-Related Differences in the Immune System Drive Differential Responses to Anti-PD-1 Immunotherapy
Biomolecules
systems biology
immune checkpoint inhibitors
sex-specific differences
personalized immunotherapy
anti-PD-1 immunotherapy
title Sex-Related Differences in the Immune System Drive Differential Responses to Anti-PD-1 Immunotherapy
title_full Sex-Related Differences in the Immune System Drive Differential Responses to Anti-PD-1 Immunotherapy
title_fullStr Sex-Related Differences in the Immune System Drive Differential Responses to Anti-PD-1 Immunotherapy
title_full_unstemmed Sex-Related Differences in the Immune System Drive Differential Responses to Anti-PD-1 Immunotherapy
title_short Sex-Related Differences in the Immune System Drive Differential Responses to Anti-PD-1 Immunotherapy
title_sort sex related differences in the immune system drive differential responses to anti pd 1 immunotherapy
topic systems biology
immune checkpoint inhibitors
sex-specific differences
personalized immunotherapy
anti-PD-1 immunotherapy
url https://www.mdpi.com/2218-273X/14/12/1513
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AT mohammadkohandel sexrelateddifferencesintheimmunesystemdrivedifferentialresponsestoantipd1immunotherapy
AT michelleprzedborski sexrelateddifferencesintheimmunesystemdrivedifferentialresponsestoantipd1immunotherapy