MSGID: 1:317/3 64a6437e
PID: hpt/lnx 1.9.0-cur 2019-01-08
TID: hpt/lnx 1.9.0-cur 2019-01-08
 Immune and tumor cell 'tug-of-war' controls anti-cancer activity 

  Date:
      July 5, 2023
  Source:
      St. Jude Children's Research Hospital
  Summary:
      Scientists have found that altering amounts of the nutrient
      glutamine in the tumor microenvironment could enhance or impair
      the immune system's anti-cancer response.


      Facebook Twitter Pinterest LinkedIN Email

==========================================================================
FULL STORY
==========================================================================
Scientists at St. Jude Children's Research Hospital found immune and
tumor cells compete over glutamine, a major nutrient in their local
environment, with significant implications for anti-cancer activity. If
cancer cells monopolize glutamine, they can prevent immune cells from
destroying cancer. The findings show that supplying glutamine directly to
tumors helps initiate the immune system's cancer-killing activity. The
researchers also identified a molecular pathway that could serve as a
potential drug target to achieve the same effect.

The findings were published today in Nature.

"It's a nutrient tug-of-war between tumor cells and immune cells,"
said corresponding author Hongbo Chi, Ph.D., St. Jude Department of
Immunology. "If tumor cells use all the available glutamine, then a
specialized immune cell type known as the dendritic cell is starved of
glutamine, leading to impaired anti-tumor immune function. But if we can
supplement enough glutamine to the tumor microenvironment, that will
inhibit tumor growth because dendritic cells will use it and activate
the adaptive immune response." Dendritic cells turn on cancer-killing
immune cells called T cells.

The group showed that resupplying glutamine in the tumor microenvironment
severely reduced tumor growth because dendritic cells were then better
able to activate anti-cancer T cells. The tumor microenvironment
is composed of chemicals and cells around cancer cells. Infamously,
cancer cells secrete many signals to turn the immune response "off" in
this area, especially the T cells that threaten their destruction. The
St. Jude team is the first to identify a nutrient as a major signal
between cancer cells and dendritic cells in this local environment.

Improving anti-cancer therapies "We are very excited to establish the link
between glutamine, therapeutic effect and dendritic cells," said first
author Chuansheng Guo, Ph.D., St. Jude Department of Immunology. "It's
critical for the efficacy of immune checkpoint blockade and adoptive
cell transfer therapy."  Immune checkpoint blockade therapy inhibits the
"off" signals cancer cells send to immune cells that suppress the immune
response in the tumor microenvironment. These therapies have been highly
effective, but only in a small number of patients. The researchers found
that supplying glutamine in combination with checkpoint therapy enhanced
anti-cancer activity in mice.

"This paper provides a proof of concept that nutrients could act
synergistically with checkpoint inhibitors for tumor treatment as a new
strategy for combination therapy," Chi said.

The mechanism of helping or hindering cancer-killing While much cancer
research has focused on T cells because of their direct cancer-killing
activity, this study is one of the first to examine how the tumor
microenvironment affects the dendritic cells, which activate T cells. The
researchers found that without glutamine, dendritic cells failed to
activate the T cells that directly kill cancer cells.

"Even though T cells are the cornerstone for anti-cancer immunity,
they cannot do the job by themselves," Chi explained. "We can think
of dendritic cells as the driver and the T cell as the car. If you
do not have a driver, the car will not move. Moreover, nutrients like
glutamine serve as the license for the driver."  Similarly, when the
researchers removed the proteins that respond to or take up glutamine
in dendritic cells, the immune cells failed to activate cancer- killing
cells. These proteins, called FLCN and SLC38A2, are important in sensing
and acquiring nutrients but have not previously been connected to immune
cells' reactions to tumors. They may serve as potent drug targets to
improve cancer therapy.

"We're extremely excited about these findings," Chi said. "In addition
to enhancing the therapeutic intervention, we have provided a conceptual
advance by showing how nutrients mediate cell-cell communication, an
understudied concept in the field of immunometabolism."  The study's
other authors are Zhiyuan You, Hao Shi, Gustavo Palacios, Cliff Guy,
Sujing Yuan, Nicole Chapman, Seon Ah Lim, Xiang Sun, Jordy Saravia,
Sherri Rankin, Yogesh Dhungana, of St. Jude, and Yu Sun and Xingrong Du,
formerly of St. Jude.

The study was supported by grants from the National Institutes of Health
(AI105887, AI131703, AI140761, AI150241, AI150514 and CA253188) and ALSAC,
the fundraising and awareness organization of St. Jude.

    * RELATED_TOPICS
          o Health_&_Medicine
                # Immune_System # Lymphoma # Brain_Tumor # Cancer #
                Lung_Cancer # Prostate_Cancer # Colon_Cancer # Skin_Cancer
    * RELATED_TERMS
          o Immune_system o Monoclonal_antibody_therapy o T_cell o
          Inflammation o Lymphoma o Chemotherapy o Incident_Command_System
          o Cancer

==========================================================================

 Print

 Email

 Share
==========================================================================
****** 1 ****** ***** 2 ***** **** 3 ****
*** 4 *** ** 5 ** Breaking this hour
==========================================================================
    * Why_Birds_Ancestors_Lived;_Other_Dinosaurs_Died *
    Dissolving_Cardiac_Device_Treats_Heart_Disease *
    Webb_Locates_Dust_Reservoirs_in_Two_Supernovae *
    Earth_Formed_from_Dry,_Rocky_Building_Blocks *
    Ancient_Volcanic_Activity_On_Moon's_Dark_Side *
    Highly_Conductive_Metallic_Gel_for_3D_Printing *
    Potent_Greenhouse_Gas_Could_Be_Abated_Today *
    Polymer_Brains_for_Artificial_Neural_Networks *
    Early_Apex_Predator_Sought_Soft_Over_...

    * Time_in_Universe_Once_Flowed_Five_Times_Slower

Trending Topics this week
==========================================================================
HEALTH_&_MEDICINE Fitness Genes Cholesterol MIND_&_BRAIN Child_Psychology
Creativity Educational_Psychology LIVING_&_WELL Fitness Healthy_Aging
Staying_Healthy


==========================================================================

Strange & Offbeat
==========================================================================
HEALTH_&_MEDICINE
Grocery_Store_Carts_Set_to_Help_Diagnose_Common_Heart_Rhythm_Disorder_and
Prevent_Stroke DNA_Can_Fold_Into_Complex_Shapes_to_Execute_New_Functions
Everyone's_Brain_Has_a_Pain_Fingerprint_--_New_Research_Has_Revealed_for_the
First_Time MIND_&_BRAIN
AI_Tests_Into_Top_1%_for_Original_Creative_Thinking
Scientists_Discover_Spiral-Shaped_Signals_That_Organize_Brain_Activity
Illusions_Are_in_the_Eye,_Not_the_Mind LIVING_&_WELL
AI_Tests_Into_Top_1%_for_Original_Creative_Thinking
Amputees_Feel_Warmth_in_Their_Missing_Hand
Why_Do_Champagne_Bubbles_Rise_the_Way_They_Do?_Scientists'_New_Discovery_Is
Worthy_of_a_Toast Story Source: Materials provided by
St._Jude_Children's_Research_Hospital. Note: Content may be edited for
style and length.


==========================================================================
Journal Reference:
   1. Guo, C., You, Z., Shi, H. et al. SLC38A2 and glutamine signalling in
      cDC1s dictate anti-tumour immunity. Nature, 2023 DOI:
      10.1038/s41586-023- 06299-8
==========================================================================

Link to news story:
https://www.sciencedaily.com/releases/2023/07/230705143007.htm

--- up 1 year, 18 weeks, 2 days, 10 hours, 50 minutes
 * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)
SEEN-BY: 15/0 106/201 114/705 123/120 153/7715 218/700 226/30 227/114
SEEN-BY: 229/110 112 113 307 317 400 426 428 470 664 700 291/111 292/854
SEEN-BY: 298/25 305/3 317/3 320/219 396/45 5075/35
PATH: 317/3 229/426