Metastasis kills most cancer patients and grows from invisible seeds. How do these seeds escape from attack by immune cells? These seeds harness stress hormones!🤯
thanks to @nyscf @parkerici for their support. Today at @Nature https://t.co/rMKnHEqQwb
Where do cancers start? In the liver, not all cells are the same. The liver is divided into 3 “zones,” and each specializes in different metabolic tasks. We show in @Science that where a mutation occurs in a liver lobule can determine a cell’s fate. https://t.co/3YTc77gZcd (1/9)
BREAKING NEWS
The 2025 #NobelPrize in Physiology or Medicine has been awarded to Mary E. Brunkow, Fred Ramsdell and Shimon Sakaguchi “for their discoveries concerning peripheral immune tolerance.”
Stellar postdoc @DebolinaGanguly and I wrote this spotlight in for a super cool paper on the systemic effects of metatasis in breast cancer. The organ of metastatic disease has a BIG impact! Highly recommended paper in @Cancer_Cell https://t.co/7qTkFD0a7t
1/ 🚨 Hot off the press in @NatImmunol: CD4⁺ T cells can license Kupffer cells to rescue dysfunctional CD8⁺ T cells in the liver. Hepatitis B virus (HBV) infection is just the proving ground—this is a paradigm shift in tissue immunity. https://t.co/C6CzH3s34y 🧵(1/11)
2/ Chronic HBV infection was the perfect stress test: intrahepatic CD8⁺ T cells are primed yet quickly stall. How to reignite them has been a major interest of our lab. (2/11)
3/ Pre‑activated helper CD4⁺ T cells solve the puzzle. They skip lymph nodes and head straight to the liver, where they form intimate triads with Kupffer cells (KCs), the resident macrophages patrolling sinusoids. (3/11)
4/ Through CD40L‑CD40 contact, those helpers re‑program KCs—turning tolerant scavengers into potent APC‑like cytokine factories. It’s on‑site immune engineering, not remote coaching. (4/11)
5/ Licensed KCs release a two‑part cocktail:
• IL‑12 expands the helper pool
• IL‑27 wakes up dysfunctional CD8⁺ T cells, restoring effector molecules and metabolic vigor. (5/11)
6/ Dendritic cells? Dispensable. Secondary lymphoid organs? Surgically removed or pharmacologically blocked—help still flows. Immunity can be fabricated in situright inside the parenchyma. (6/11)
7/ Remove KCs and the circuit collapses; block CD40L or IL‑27 and CD8⁺ T cells relapse into lethargy. The essential loop is:
CD4 T cell ➜ KC ➜ IL‑27 ➜CD8 T cell. (7/11)
8/ IL‑27 isn’t just necessary—it’s sufficient. Recombinant IL‑27 revived antiviral CD8⁺ activity in mice and super‑charged HBV‑specific T cells from patients. (8/11)
9/ Why care beyond HBV? Tapping a CD4–IL‑27 axis could be a universal key to re‑arming liver‑resident CD8⁺ T cells against infections and cancer (9/11)
10/ The work reframes “CD4 help”: not a lymph‑node pep talk but an on‑site renovation that overrides local tolerance. Therapeutics that mimic KC licensing could deliver potency where it’s needed and spare the rest of the body. (10/11)
11/ Kudos to Valentina Venzin, Cristian Beccaria, all members of the @IannaconeLab & collaborators for charting this intrahepatic circuit. Expect Kupffer‑cell licensing and IL‑27 to enter conversations on cancer immunotherapy, vaccines and beyond. Thoughts welcome! 🙌
@ImmunoPodcast@profvrr@ERC_Research@EMBO@EMBO_YIP@ArmeniseHarvard@AIRC_it@MyUniSR@SanRaffaeleMI
(11/11)
#UTSW biochemist Zhijian "James" Chen, Ph.D., wins the Albert Lasker Basic Medical Research Award, sometimes called “America’s Nobel,” for his discovery of the cGAS enzyme, which senses invading pathogens and triggers immune response. https://t.co/q7NWqorgja @LaskerFDN
Debolina Ganguly, PhD (@debog93), a 2024 Parker Scholar at @DanaFarber, studies how metastatic stem cells promote systemic tolerance to tumor antigens & suppress responses to immunotherapy, advancing understanding of patient response. Hear more about PICI’s support of her work.
Thrilled and honored to be a named a Parker Scholar! Very excited to be a part of the PICI network. Grateful for the support of my incredible mentor @JudithAgudo1 and the PICI leadership @DanaFarber
PICI is thrilled to award over $1 million in total to our 2024 class of Early Career Researcher recipients. These bold investigators are propelling #immunotherapy w/ pioneering research that could lead to breakthrough discoveries. Meet the 2024 awardees: https://t.co/Ta2zZfwYUP