Sex-Driven Differences in Immunological Responses: Challenges and Opportunities for the Immunotherapies of the Third Millennium

Mirandola, Leonardo; Wade, Raymond; Verma, Rashmi; Peña, Camilo; Hosiriluck, Nattamol; Figueroa, José A.; Cobos, Everardo; Jenkins, Marjorie; Chiriva‐Internati, Maurizio

doi:10.3109/08830185.2015.1018417

Cited by 40 publications

(29 citation statements)

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“…The statistically significant correlation between sex and median OS at multivariate analysis, in favor of female patients, remains partly unexplained, and needs further confirmations. Even if it starts to be known that there are sex-driven differences in immunological responses, which could bring to different patterns of response to immunotherapy for male and female patients [44], as Table 1 shows, male and female populations were unbalanced in two important categories: primary tumors (e.g., more NSCLC among male patients and more melanoma among female patients) and number of metastatic sites. Among limits of the present study, the retrospective design with its selection biases, could partly explain that clinical outcomes in overall population are higher than what is generally reported with anti-PD-1/PD-L1 agents.…”

Section: Discussionmentioning

confidence: 99%

Family History of Cancer as Surrogate Predictor for Immunotherapy with Anti-Pd1/Pd-L1 Agents: Preliminary Report of the Fami-L1 Study

et al. 2018

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Aim: Tumors related to hereditary susceptibility seem to have an immunosensitive phenotype. Materials & methods : We conducted a multicenter retrospective study, to investigate if family history of cancer, multiple neoplasms and early onset of cancer could be related to clinical outcomes of anti-PD-1/PD-L1 therapy. Activity and efficacy data of 211 advanced cancer patients (kidney, non-small-cell lung cancer, melanoma, urothelium, colorectal and HeN), treated at seven Italian centers with anti-PD-1/PD-L1 agents, were analyzed. Results: In this preliminary report at multivariate analyses, positive family history of cancer showed a statistically significant relationship with a better objective response rate (p = 0.0024), disease control rate (p = 0.0161), median time to treatment failure (p = 0.0203) and median overall survival (p = 0.0221). Diagnosis of multiple neoplasms significantly correlates only to a better disease control rate, while interestingly non-early onset of cancer and sex (in favor of female patients) showed significant correlation with a better median overall survival (p = 0.0268 and p = 0.0272, respectively). Conclusion: This pilot study seems to individuate easily available patient's features as possible predictive surrogates of clinical benefit for anti-PD-1/PD-L1 treatments. These preliminary results need to be confirmed with a greater sample size, in prospective trials with immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Family History of Cancer as Surrogate Predictor for Immunotherapy with Anti-Pd1/Pd-L1 Agents: Preliminary Report of the Fami-L1 Study

et al. 2018

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“…In addition to higher titers of immunoglobulins women have a higher frequency of circulating CD4+ T cells than men. The CD4+ T cell count appears to be an important factor associated with the development of KS in patients with AIDS-related KS [20]. Human herpesvirus-8 infection is required in KS pathogenesis but is not enough to cause KS.…”

Section: Discussionmentioning

confidence: 99%

Retrospective Analysis of 91 Kaposi’s Sarcoma Cases: A Single-Center Experience and Review of the Literature

Yazıcı¹,

Zorlu²,

Başkan³

et al. 2018

Dermatology

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Background: Kaposi’s sarcoma (KS) is a multifocal angioproliferative tumor involving primarily the skin. Objective: The aim of this study was to describe the clinical, demographic, histopathological characteristics, treatment modalities, and outcome of 91 KS patients, and compare them with other contemporary research. Methods: Medical records of 91 KS patients followed between January 2005 and September 2017 were evaluated retrospectively. Results: Most of our patients were male (male-to-female ratio was 4.05). The median age at diagnosis was 69 years (range, 6–93 years). The duration of the lesions varied between 3 and 25 years. The lower extremities were the most commonly involved area (51.6%). Of the 91 patients, classic type KS was seen in 75 patients. Radiotherapy was used successfully in approximately half of our patients. Recurrence was observed in approximately one third of the patients. All KS patients in this study except 1 were classic KS. Conclusion: The clinical and demographic characteristics of our patients were compatible with the previous literature suggesting that KS is a tumor that tends to be limited to the skin. Close follow-up of patients is important to monitor for recurrence. This is the largest report from Turkey to date.

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“…Males and females often exhibit differences in the peripheral immune activation to a given stimulus, with females generally having a greater response (see Mirandola et al, 2015 for review). This may explain why women have a higher incidence of most autoimmune diseases (Beeson, 1994; Whitacre et al, 1999), including those that affect the brain such as multiple sclerosis (MS).…”

Section: Role Of the Immune Systemmentioning

confidence: 99%

“…In addition to immune cells residing within the brain, there are sex differences in peripheral immune responses that can affect normal brain function and the susceptibility to disease (De Vries and Forger, 2015; Mirandola et al, 2015; Spence and Voskuhl, 2012). Moreover, just recently, functional lymphatic vessels were discovered that are embedded in the dura and drain to cervical lymph nodes (Louveau et al, 2015).…”

Section: Where Do We Go From Here?mentioning

confidence: 99%

Cellular and molecular mechanisms of sexual differentiation in the mammalian nervous system

Forger

Strahan

Castillo‐Ruiz

2016

Frontiers in Neuroendocrinology

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Neuroscientists are likely to discover new sex differences in the coming years, spurred by the National Institutes of Health initiative to include both sexes in preclinical studies. This review summarizes the current state of knowledge of the cellular and molecular mechanisms underlying sex differences in the mammalian nervous system, based primarily on work in rodents. Cellular mechanisms examined include neurogenesis, migration, the differentiation of neurochemical and morphological cell phenotype, and cell death. At the molecular level we discuss evolving roles for epigenetics, sex chromosome complement, the immune system, and newly identified cell signaling pathways. We review recent findings on the role of the environment, as well as genome-wide studies with some surprising results, causing us to rethink often-used models of sexual differentiation. We end by pointing to future directions, including an increased awareness of the important contributions of tissues outside of the nervous system to sexual differentiation of the brain.

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Sex-Driven Differences in Immunological Responses: Challenges and Opportunities for the Immunotherapies of the Third Millennium

Abstract: Future clinical trials focusing on cancer immunotherapy will need to take into account the differences in the immune response and in the frequency of target antigen expression between male and females, in order to optimize these anti-cancer immunotherapies of the third millennium.

Cited by 40 publications

References 40 publications

Family History of Cancer as Surrogate Predictor for Immunotherapy with Anti-Pd1/Pd-L1 Agents: Preliminary Report of the Fami-L1 Study

Family History of Cancer as Surrogate Predictor for Immunotherapy with Anti-Pd1/Pd-L1 Agents: Preliminary Report of the Fami-L1 Study

Retrospective Analysis of 91 Kaposi’s Sarcoma Cases: A Single-Center Experience and Review of the Literature

Cellular and molecular mechanisms of sexual differentiation in the mammalian nervous system

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