The Batlle Lab
@batllelab.bsky.social
We work on minimal residual disease and metastasis by colorectal cancer from the perspective of cancer stem cells and their interaction with the tumor microenvironment.
@IRBBarcelona,bsky.social
@IRBBarcelona,bsky.social
This is a major finding by various independent teams.
Cell Plasticity could be exploited therapeutically
Please see also aacrjournals.org/cancerdiscov...
Cell Plasticity could be exploited therapeutically
Please see also aacrjournals.org/cancerdiscov...
A plastic EMP1⁺ to LGR5⁺ cell state conversion as a bypass to KRAS-G12D pharmacological inhibition in metastatic colorectal cancer
Abstract. Inhibitors of the oncogene KRAS hold promise for treating metastatic CRC (mCRC). Here we show that a selective, covalent small molecule inhibitor of the active (ON) conformation of RAS-G12D,...
aacrjournals.org
November 26, 2025 at 4:07 PM
This is a major finding by various independent teams.
Cell Plasticity could be exploited therapeutically
Please see also aacrjournals.org/cancerdiscov...
Cell Plasticity could be exploited therapeutically
Please see also aacrjournals.org/cancerdiscov...
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
📖 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
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...
www.nature.com
November 7, 2025 at 12:30 PM
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
📖 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.
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.
November 7, 2025 at 12:30 PM
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.
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.
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.
November 7, 2025 at 12:30 PM
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.
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
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
November 7, 2025 at 12:30 PM
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
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
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
November 7, 2025 at 12:30 PM
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
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).
We validated these findings in liver metastases generated by mouse tumor organoids carrying 3 or 4 driver mutations (Apc, Kras, Trp53, ±Tgfbr2 or Smad4).
November 7, 2025 at 12:30 PM
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).
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.
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.
November 7, 2025 at 12:30 PM
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.
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.
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.
November 7, 2025 at 12:30 PM
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.
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).
In parallel, single-cell profiling of the myeloid compartment revealed that TGFβ instructs an immunosuppressive macrophages population characterized by the expression of SPP1 (osteopontin).
November 7, 2025 at 12:30 PM
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).
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
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
November 7, 2025 at 12:30 PM
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
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.
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.
November 7, 2025 at 12:30 PM
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.
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.
@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.
November 7, 2025 at 12:30 PM
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.
@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.
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.
November 7, 2025 at 12:30 PM
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.
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.
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?
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?
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.
www.nature.com
November 7, 2025 at 12:30 PM
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?
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 🔝🔝🙌🙌
👌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 🔝🔝🙌🙌
November 7, 2025 at 12:30 PM
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 🔝🔝🙌🙌
👌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 🔝🔝🙌🙌