Key characteristics of immune cells in ovarian cancer
Tissue-resident memory T cells are important mediators of immune response


Date:
April 14, 2022
Source:
H. Lee Moffitt Cancer Center & Research Institute
Summary:
Researchers want to improve their understanding of the immune
environment in ovarian cancer in hopes of making immunotherapy
an option for these patients. Researchers now report on key
characteristics of immune cells in ovarian cancer and identify
cell types important for mediating an immune response.



FULL STORY ========================================================================== Ovarian cancer is a difficult to diagnose malignancy that is often caught
at a more advanced stage. Treatments for this cancer have changed little
over the past few decades, with surgery and chemotherapy being the most
common therapeutic approaches. Immunotherapy, a type of treatment that activates a patient's immune system to target cancer cells, has been
successful in many diseases but not ovarian cancer and it is unclear why.


========================================================================== Researchers at Moffitt Cancer Center want to improve their understanding
of the immune environment in ovarian cancer in hopes of making
immunotherapy an option for these patients. In a new study published
inCancer Cell, they report on key characteristics of immune cells
in ovarian cancer and identify cell types important for mediating an
immune response.

Checkpoint inhibitors are a specific type of immunotherapy that work
by activating an immune cell called T cells. In order for checkpoint
inhibitors to work, patients must have T cells that are ready to be
activated in close proximity to tumor cells. Ovarian cancer is considered
a type of tumor that should be impacted by checkpoint inhibitors because
of T cell presence; yet clinical studies in ovarian cancer for these
drugs have not been successful.

Moffitt researchers, led by Immunology Department Chair Jose
Conejo-Garcia, M.D., Ph.D., wanted to determine whether ovarian cancer
has the proper T cells to initiate an immune response and characterize
the properties of the T cells present within ovarian cancer tumors. They performed a comprehensive analysis of ovarian cancer patient samples at
the single-cell and tissue levels. They discovered that ovarian cancer
is an immunogenic type of tumor that should be impacted by drugs that
activate the immune system; however, immune activity against tumor cells
is dependent on a small subset of immune cells.

The researcher team analyzed the types of T cells present in ovarian
tumors and discovered that tissue-resident memory like T cells do a
better job of recognizing tumor cells than T cells that are circulating
and infiltrating the tumor. They also discovered that tissue-resident
memory like T cells arise from circulating T cells and undergo
a differentiation process into a tissue- resident memory stem cell
that can generate T cells that actively target cancer cells. Some of
these active T cells will eventually differentiate into an exhausted, inactivated state. The researchers confirmed that tissue-resident memory
stem cells were important for anti-tumor immune activity by demonstrating
that high numbers of them were associated with improved patient survival
in ovarian cancer.

Interestingly, some of these lymphocytes show features of trogocytosis,
a process where T cells take up a chunk of the membrane of target tumor
cells. A trajectory of differentiation of tissue-resident memory T cells
from stemness to irreversible exhaustion, in addition to evidence of
trogocytic activity, identifies the T cells truly relevant to determine
ovarian cancer patients' outcome.

These results demonstrate that ovarian cancer, despite resistance to
existing immunotherapies, is indeed an immunogenic disease and provide
a roadmap for the design of improved immunotherapy options, which could
be applicable to other tumors with similar mutational burden.

This study was supported by the National Institutes of Health
(R01CA157664, R01CA124515, R01CA178687, R01CA211913, U01CA232758,
R01CA184185, RO1CA262121, T32CA009140, P30CA076292) and the American
Cancer Society.


========================================================================== Story Source: Materials provided by H._Lee_Moffitt_Cancer_Center_&_Research_Institute. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Carmen M. Anadon, Xiaoqing Yu, Kay Ha"nggi, Subir Biswas, Ricardo A.

Chaurio, Alexandra Martin, Kyle K. Payne, Gunjan Mandal, Patrick
Innamarato, Carly M. Harro, Jessica A. Mine, Kimberly B. Sprenger,
Carla Cortina, John J. Powers, Tara Lee Costich, Bradford A. Perez,
Chandler D.

Gatenbee, Sandhya Prabhakaran, Douglas Marchion, Mirjam
H.M. Heemskerk, Tyler J. Curiel, Alexander R. Anderson, Robert
M. Wenham, Paulo C.

Rodriguez, Jose R. Conejo-Garcia. Ovarian cancer immunogenicity is
governed by a narrow subset of progenitor tissue-resident memory
T cells.

Cancer Cell, 2022; DOI: 10.1016/j.ccell.2022.03.008 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220414125103.htm

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