The Batlle Lab

🙏Thank you to Ràdio Barcelona for the Toresky Award 🎙️
🏆Although it recognizes a “personality,” the lab’s discoveries are the result of my team’s dedication and passion
🥼PhDs, postdocs, & senior members work relentlessly to make possible the breakthroughs being recognized today 🙌
✨Huge thanks to all

Leuven at this time of the year was an extra bonus.

Tumor Heterogeneity, Plasticity and Therapy (3rd edition) 10-12 December 2025, Leuven, Belgium

At the Tumor Heterogeneity, Plasticity & Therapy conference in Leuven! 🌟🇧🇪 Huge thanks to the organizers for the invitation. 🙌

Tumour heterogeneity and plasticity are critical areas that are reshaping how we understand therapy resistance and tumour evolution.🔬

www.vibconferences.be/events/tumor...

Yesterday in Valencia Dr. @nlbigas.bsky.social received the 2025 Premio Rei Jaume I in Biomedical Research. Her work on how cancer mutations arise and evolve has earned major recognition!
Congratulations, Núria! 🙌
#ReiJaumeI #CancerResearch
@cerca.cat @icreacommunity.bsky.social @bbglab.bsky.social

This is a major finding by various independent teams.

Cell Plasticity could be exploited therapeutically

Please see also aacrjournals.org/cancerdiscov...

PODCAST: Conversaciones del Premio Nobel
Producida por Nobel Prize Outreach y la @fundacionareces.bsky.social, los podcast de la serie "Conversaciones del Premio Nobel " proponen acercar a la sociedad española los logros de estos científicos y sus historias personales.

TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1+ macrophages - Nature Genetics Targeting TGFBR1 in transplantable mouse colorectal tumor organoids improves response to anti-PD-L1 therapy. Mechanistically, TGF-β abrogates clonal expansion of T effector and memory phenotypes and i...

1/17 🧵
🙌Thrilled to share our first hard-core immunology paper out today in Nature Genetics! 👇

➡️We unravel how TGFβ suppresses the innate and adaptive immune system in microsatellite stable colorectal cancer (MSS CRC).

Very proud of the team and efforts behind it.

www.nature.com/articles/s41...

Our recent Cancer Discovery study (Centonze et al.) shows that within hours, metastatic CRC cells switch from an EMP1⁺ invasive state to an LGR5⁺ stem-like program, highlighting that Plasticity is a dynamic, regulated cell-state decision

#Bluetorial below👇🏼

#KRAS #Plasticity #ColorectalCancer

⏳Countdown to the 14th #CNAGSymposium!
🗣️Don’t miss Dr. Eduard Batlle from @irbbarcelona.org (@icreacommunity.bsky.social), sharing his insights on “Plasticity, therapy resistance, and immune evasion in metastatic colorectal cancer”

🗓️Dec 16, BCN
📎 www.cnag.eu/events/14th-...
@batllelab.bsky.social

Likewise!!!! 🙌🏼

🧵1/17

📣Thrilled to share our latest study just out in Cancer Discovery!

➡️
aacrjournals.org/cancerdiscov...

🔬 #ColorectalCancer evades #immunotherapy using a dual barrier:

A study by #IRBBarcelona & @cnag-eu.bsky.social reveals how metastatic colorectal tumours block the immune system through two complementary mechanisms.

📰 @natgenet.nature.com

➡️ bit.ly/49BJaC0

#IRBScience @batllelab.bsky.social

🧪

TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1+ macrophages - Nature Genetics Targeting TGFBR1 in transplantable mouse colorectal tumor organoids improves response to anti-PD-L1 therapy. Mechanistically, TGF-β abrogates clonal expansion of T effector and memory phenotypes and i...

17/17

📖 Read the paper: Henriques et al., Nature Genetics

“TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1 macrophages.”
www.nature.com/articles/s41...

➡️Full Text available here: rdcu.be/eOLi6

16/17

This research was supported by the @erc.europa.eu, the Asociación Española Contra el Cáncer (AECC), @caixaresearch.bsky.social , Worldwide Cancer Research, La Marató de TV3, CIBERONC, AGAUR, Fundación Olga Torres, and the Spanish Ministry of Science and Innovation.

15/17

We thank all members of the BatlleLab and our collaborators @irbbarcelona.org & @cnag-eu.bsky.social. Special mention to A. Riera and C. Sanchez for TGFβ inhibitor synthesis. We acknowledge the dedication of technical platforms, the bioinformatic unit, and the animal facility.

14/17
Our work shows that TGFβ coordinates immune suppression across the adaptive and innate compartments, generating a two-layer defense that tumors use to resist immunotherapy.
Breaking this dual barrier — targeting TGFβ alongside PD-1/PD-L1 — can turn CRCs into immunotherapy-sensitive disease

13/17

TGFβ inhibition (via SMIs: galunisertib, LY3200882, or vactosertib) had dramatic effects on these models:
✅ It dismantled the collagen network produced by CAFs
✅It opened the path for peripheral CD8⁺ T cells to enter metastatic lesions
✅It made refractory tumors responsive to aPD-L1 therapy

12/17

We validated these findings in liver metastases generated by mouse tumor organoids carrying 3 or 4 driver mutations (Apc, Kras, Trp53, ±Tgfbr2 or Smad4).

11/17
In the absence of Osteopontin - (Spp1 KO) - metastases remained T cell infiltrated and checkpoint blockade exerted potent therapeutic responses, suggesting therapeutic agents against Osteopontin, could be tested as a proxy for TGFβ inhibition.

10/17

By generating macrophage-specific Tgfbr2 knockout mice, Ana Henriques showed that this population limits T cell proliferation in the TME.

📌Remarkably, we discovered that SPP1 production is necessary for this immunosuppressive macrophage response.

9/17

In parallel, single-cell profiling of the myeloid compartment revealed that TGFβ instructs an immunosuppressive macrophages population characterized by the expression of SPP1 (osteopontin).

8/17
Meanwhile, aPD-L1 did something remarkable but incomplete: it boosted T cell motility allowing infiltrated cells to move and engage targets.
TGFβ inhibition enabled their entry but not their movement.

✅Only combination therapy achieved both, unleashing a fully active antitumor immune response

7/17

In experimental models of advanced colorectal cancer (CRC), we showed that TGFβ signaling on T cells prevented the influx of memory-like T cells from the lymph nodes into the metastatic TME.

🔴Without TGFβ inhibition, the number of T cells is insufficient to eradicate metastatic disease.

6/17

@hoheyn.bsky.social and @paulanietog.bsky.social identified diverse CD8⁺ T cell states — from naïve-like and progenitor to effector and exhausted — and together with Maria Salvany-Celades, they traced how TGFβ inhibition restores clonal expansion and effector differentiation.

5/17

To understand the immune landscape at single-cell resolution, @hoheyn.bsky.social and @paulanietog.bsky.social from @cnag-eu.bsky.social led an extensive scRNA-seq + TCR-seq analysis of tumor-infiltrating lymphocytes (TILs) and myeloid cells in models of metastatic CRC under treatment.

TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis - Nature A combination of TGFβ inhibition and checkpoint-inhibition therapy provokes a potent cytotoxic response against metastatic tumours derived from colorectal cancers in mice.

4/17

We had shown that TGFβ inhibition in CRC enabled T cell infiltration & synergized with immune checkpoint blockade to eradicate metastases 👇.
www.nature.com/articles/nat...

➡️Now we dove into the immunology of metastatic disease: how does TGFβ inhibition reshape the immune landscape of mets?

3/
👌A tremendous team effort led by Ana Henriques, Maria Salvany-Celades, & Alejandro Prados in the BatlleLab, in collaboration with @paulanietog.bsky.social and @hoheyn.bsky.social, with the help of amazing multidisciplinary teams at @irbbarcelona.org, and @cnag-eu.bsky.social.

Kudos to all 🔝🔝🙌🙌

TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1+ macrophages - Nature Genetics Targeting TGFBR1 in transplantable mouse colorectal tumor organoids improves response to anti-PD-L1 therapy. Mechanistically, TGF-β abrogates clonal expansion of T effector and memory phenotypes and i...

2/17
Through genetic dissection in model systems of advanced CRC, integrated single-cell profiling, and analyses of patient data, we reveal that TGFβ builds a dual immune barrier that blocks both the recruitment and expansion of memory T cells in liver metastases.
www.nature.com/articles/s41...

TGF-β builds a dual immune barrier in colorectal cancer by impairing T cell recruitment and instructing immunosuppressive SPP1+ macrophages - Nature Genetics Targeting TGFBR1 in transplantable mouse colorectal tumor organoids improves response to anti-PD-L1 therapy. Mechanistically, TGF-β abrogates clonal expansion of T effector and memory phenotypes and i...

1/17 🧵
🙌Thrilled to share our first hard-core immunology paper out today in Nature Genetics! 👇

➡️We unravel how TGFβ suppresses the innate and adaptive immune system in microsatellite stable colorectal cancer (MSS CRC).

Very proud of the team and efforts behind it.

www.nature.com/articles/s41...