• Study reveals male sex hormones are new

    From ScienceDaily@1:317/3 to All on Fri Apr 15 22:30:40 2022
    Study reveals male sex hormones are new targets for cancer immunotherapy


    Date:
    April 15, 2022
    Source:
    Ohio State University Comprehensive Cancer Center
    Summary:
    A study examined the differences in intratumoral immune responses
    between male and female cancers of non-reproductive origin.



    FULL STORY ========================================================================== Patients with cancers stemming from non-reproductive organs, such as
    bladder and liver cancer, have striking discrepancies in incidence, progression, response to treatment and survival outcomes depending on
    their sex. In almost all cases, male patients have worse prognoses
    and outcomes. This phenomenon has puzzled the scientific community
    for decades.


    ==========================================================================
    A study published today in Science Immunology and led by researchers
    in the Pelotonia Institute for Immuno-Oncology (PIIO) at The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital
    and Richard J.

    Solove Research Institute (OSUCCC -- James) examined the differences in intratumoral immune responses between male and female cancers of non- reproductive origin The focus of this research was the T cell immune
    response to malignancy, a key determinator of outcomes in cancer, and
    an important target that has contributed to the renaissance of cancer immunotherapy seen in recent years.

    The study reported a landmark finding that describes how male sex
    hormones contribute to cancer-related sex bias via the modulation of CD8+
    T cells -- a population of cells often referred to as cancer "killer"
    cells, which mediate adaptive immunity and are critical for mounting an anti-tumor response.

    "Collectively, these findings highlight androgen-mediated promotion
    of CD8+ T cell dysfunction in cancer and suggest broader implications
    for therapeutic development to address sex disparities in health and
    disease," said the study's senior corresponding author Dr. Zihai Li,
    cancer immunologist, medical oncologist and founding director of the
    PIIO at OSUCCC -- James.

    Androgens are sex hormones more highly present in males. This study
    revealed that CD8+ T cells from cancers in male subjects, including human patients and mice, are more likely to have characteristics of a weakened anti-tumor immune function, also known as "exhausted" T cells. Androgen signaling promotes the progenitor exhausted CD8+ T cell phenotype via modulating expression of TCF1, a master regulator of CD8+ T cell function.

    "Androgen-mediated promotion of CD8+ T cell dysfunction results in faster
    tumor growth and worsened outcomes, and targeting of this signaling
    cascade holds a crucial key to improving current cancer immunotherapies,"
    said Li, who is also a professor in the Ohio State College of Medicine.

    This work was made possible because of the unique collaborations happening
    in Ohio State's Pelotonia Institute for Immuno-Oncology. Founded in 2019,
    the PIIO is a comprehensive bench-to-bedside research initiative focused
    on harnessing the body's immune system to fight cancer at all levels --
    from prevention to treatment and survivorship. The institute is centered
    on systems and translational immuno-oncology and supported by immune
    monitoring and discovery as well as immuno-informatics.

    The PIIO was established through a $102 million pledge from OSUCCC --
    James and Pelotonia. Founded in 2008, Pelotonia was established with
    the objective to fund innovative cancer research, and has raised over
    $236 million for cancer research.

    Additional financial support for the study came from the National
    Institutes of Health, Prostate Cancer Foundation, Canadian Institutes
    of Health Research and Hollings Cancer Center.

    Other study authors include Hyunwoo Kwon, Johanna Schafer, No-Joon
    Song, Satoski Kaneko, Anqi Li, Tong Xiao, Anjun Ma, Carter Allen,
    Komal Das, Lei Zhou, Brian Riesenberg, Yuzhou Chang, Payton Weltge,
    Maria Velegraki, David Oh, Lawrence Fong, Qin Ma and Debasish Sundi,
    as well as co-corresponding authors Drs. Xue Li (Cedars-Sinai Medical
    Center) and Dongjun Chung (OSUCCC -- James).


    ========================================================================== Story Source: Materials provided by Ohio_State_University_Comprehensive_Cancer_Center. Note: Content may be
    edited for style and length.


    ========================================================================== Journal Reference:
    1. Hyunwoo Kwon, Johanna M. Schafer, No-Joon Song, Satoshi Kaneko,
    Anqi Li,
    Tong Xiao, Anjun Ma, Carter Allen, Komal Das, Lei Zhou, Brian
    Riesenberg, Yuzhou Chang, Payton Weltge, Maria Velegraki, David
    Y. Oh, Lawrence Fong, Qin Ma, Debasish Sundi, Dongjun Chung, Xue
    Li, Zihai Li. Androgen conspires with the CD8+ T cell exhaustion
    program and contributes to sex bias in cancer. Science Immunology,
    2022; DOI: 10.1126/sciimmunol.abq2630 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220415112152.htm

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