Induc­ing Immuno­genic Ter­tiary Lym­phoid Struc­tures Across Can­cers by Den­drit­ic Cell Reprogramming

Camille Chate­lain, Ervin Ascic, Gaia Fonta­nari, César Pérez Bucio, Maria Thrasyvoulou, Lin­meng Zhang, Vik­to­ria Kar­ali, Tom­ma­so Bal­loc­ci, Maria de Rosa Tor­res, Ste­vanus Jonathan, Anna Dara­bi, Johan Beng­zon, Ilia Kurochkin, Car­los-Fil­ipe Pereira

Ter­tiary lym­phoid struc­tures (TLS) in tumors are asso­ci­at­ed with improved respons­es to immunother­a­py, yet their con­trolled induc­tion remains elu­sive. We have devel­oped an approach repro­gram­ming tumor cells in vivo into type‑1 con­ven­tion­al den­drit­ic cell (cDC1) – like cells to rewire the tumor microen­vi­ron­ment and ini­ti­ate de novo for­ma­tion of immuno­genic TLS (imgTLS) in melanoma, colon, blad­der, breast and pan­cre­at­ic can­cer across dif­fer­ent genet­ic backgrounds.

cDC1-like cells acti­vat­ed lym­pho­tox­in, TNF, and inter­fer­on pro­grams, engaged ear­ly with T cells and required CD40 sig­nal­ing to induce mature imgTLS con­tain­ing BCL6⁺ ger­mi­nal cen­ters, inde­pen­dent­ly of endoge­nous cDC1. Spa­tial tran­scrip­tomics revealed DC-LAMP+ CCR7⁺ migra­to­ry cDC1 pro­grams, nucle­at­ing immune nich­es enriched in CD4⁺, CD8⁺ T cells, and B cells. ImgTLS sus­tained B cell-sup­port­ed T cell respons­es and pro­mot­ed sys­temic immu­ni­ty by clon­al expan­sion in absco­pal tumors.

Our study place cDC1 at the apex of TLS induc­tion and estab­lish cel­lu­lar repro­gram­ming as a gen­er­al­iz­able mech­a­nism to engi­neer lym­phoid nich­es with­in tumors and over­come resis­tance to immunotherapy.

Camille Chate­lain, Ervin Ascic, Gaia Fonta­nari, César Pérez Bucio, Maria Thrasyvoulou, Lin­meng Zhang, Vik­to­ria Kar­ali, Tom­ma­so Bal­loc­ci, Maria de Rosa Tor­res, Ste­vanus Jonathan, Anna Dara­bi, Johan Beng­zon, Ilia Kurochkin, Car­los-Fil­ipe Pereira

Ter­tiary lym­phoid struc­tures (TLS) in tumors are asso­ci­at­ed with improved respons­es to immunother­a­py, yet their con­trolled induc­tion remains elu­sive. We have devel­oped an approach repro­gram­ming tumor cells in vivo into type‑1 con­ven­tion­al den­drit­ic cell (cDC1) – like cells to rewire the tumor microen­vi­ron­ment and ini­ti­ate de novo for­ma­tion of immuno­genic TLS (imgTLS) in melanoma, colon, blad­der, breast and pan­cre­at­ic can­cer across dif­fer­ent genet­ic backgrounds.

cDC1-like cells acti­vat­ed lym­pho­tox­in, TNF, and inter­fer­on pro­grams, engaged ear­ly with T cells and required CD40 sig­nal­ing to induce mature imgTLS con­tain­ing BCL6⁺ ger­mi­nal cen­ters, inde­pen­dent­ly of endoge­nous cDC1. Spa­tial tran­scrip­tomics revealed DC-LAMP+ CCR7⁺ migra­to­ry cDC1 pro­grams, nucle­at­ing immune nich­es enriched in CD4⁺, CD8⁺ T cells, and B cells. ImgTLS sus­tained B cell-sup­port­ed T cell respons­es and pro­mot­ed sys­temic immu­ni­ty by clon­al expan­sion in absco­pal tumors.

Our study place cDC1 at the apex of TLS induc­tion and estab­lish cel­lu­lar repro­gram­ming as a gen­er­al­iz­able mech­a­nism to engi­neer lym­phoid nich­es with­in tumors and over­come resis­tance to immunotherapy.

Inducing Immunogenic Tertiary Lymphoid Structures Across Cancers by Dendritic Cell Reprogramming
Inducing Immunogenic Tertiary Lymphoid Structures Across Cancers by Dendritic Cell Reprogramming
Inducing Immunogenic Tertiary Lymphoid Structures Across Cancers by Dendritic Cell Reprogramming

Camille Chate­lain

Camille Chate­lain is a Marie Skłodows­ka-Curie post­doc­tor­al researcher in the Pereira lab in Lund Stem Cell Cen­ter (LSCC, Swe­den). Her research cen­ters on remod­el­ing the tumor microen­vi­ron­ment with immunother­a­pies. Dur­ing her PhD in the Research Cen­ter for Can­cerol­o­gy and Inte­grat­ed Immunol­o­gy of Nantes-Angers (CRCI2NA, France), she inves­ti­gat­ed the use of oncolyt­ic virus­es to mod­u­late tumor-asso­ci­at­ed macrophages toward anti-tumor phe­no­types. She then secured a Marie Skłodows­ka-Curie Action grant to join Fil­ipe Pereira’s team in Sweden. 

Her cur­rent work uti­lizes direct cell fate con­ver­sion to explore inter­ac­tions between T cells and repro­grammed den­drit­ic cells pre­sent­ing tumor anti­gens. Notably, her post­doc­tor­al research iden­ti­fied cDC1 cells as the main dri­vers of ter­tiary lym­phoid struc­ture for­ma­tion, an area she con­tin­ues to inves­ti­gate. Through col­lab­o­ra­tion with Asgard Ther­a­peu­tics, her research con­tributes direct­ly to the clin­i­cal trans­la­tion of in vivo cell repro­gram­ming strate­gies for the ben­e­fit of can­cer patients.

More about Camille Chate­lain.

Camille Chate­lain is a Marie Skłodows­ka-Curie post­doc­tor­al researcher in the Pereira lab in Lund Stem Cell Cen­ter (LSCC, Swe­den). Her research cen­ters on remod­el­ing the tumor microen­vi­ron­ment with immunother­a­pies. Dur­ing her PhD in the Research Cen­ter for Can­cerol­o­gy and Inte­grat­ed Immunol­o­gy of Nantes-Angers (CRCI2NA, France), she inves­ti­gat­ed the use of oncolyt­ic virus­es to mod­u­late tumor-asso­ci­at­ed macrophages toward anti-tumor phe­no­types. She then secured a Marie Skłodows­ka-Curie Action grant to join Fil­ipe Pereira’s team in Sweden. 

Her cur­rent work uti­lizes direct cell fate con­ver­sion to explore inter­ac­tions between T cells and repro­grammed den­drit­ic cells pre­sent­ing tumor anti­gens. Notably, her post­doc­tor­al research iden­ti­fied cDC1 cells as the main dri­vers of ter­tiary lym­phoid struc­ture for­ma­tion, an area she con­tin­ues to inves­ti­gate. Through col­lab­o­ra­tion with Asgard Ther­a­peu­tics, her research con­tributes direct­ly to the clin­i­cal trans­la­tion of in vivo cell repro­gram­ming strate­gies for the ben­e­fit of can­cer patients.

Camille Chatelain | Inducing Immunogenic Tertiary Lymphoid Structures Across Cancer Types With Dendritic Cell Reprogramming
Camille Chate­lain, Lund Uni­ver­si­ty, SWEDEN

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