Type 1 interferon mediated signaling is indispensable for eliciting anti-tumor responses by Mycobacterium indicus pranii
IntroductionThe evolving tumor secretes various immunosuppressive factors that reprogram the tumor microenvironment (TME) to become immunologically cold. Consequently, various immunosuppressive cells like Tregs are recruited into the TME which in turn subverts the anti-tumor response of dendritic ce...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1104711/full |
| _version_ | 1827967575021060096 |
|---|---|
| author | Gargi Roy Anush Chakraborty Bharati Swami Lalit Pal Charvi Ahuja Soumen Basak Sangeeta Bhaskar |
| author_facet | Gargi Roy Anush Chakraborty Bharati Swami Lalit Pal Charvi Ahuja Soumen Basak Sangeeta Bhaskar |
| author_sort | Gargi Roy |
| collection | DOAJ |
| description | IntroductionThe evolving tumor secretes various immunosuppressive factors that reprogram the tumor microenvironment (TME) to become immunologically cold. Consequently, various immunosuppressive cells like Tregs are recruited into the TME which in turn subverts the anti-tumor response of dendritic cells and T cells.Tumor immunotherapy is a popular means to rejuvenate the immunologically cold TME into hot. Mycobacterium indicus pranii (MIP) has shown strong immunomodulatory activity in different animal and human tumor models and has been approved for treatment of lung cancer (NSCLC) patients as an adjunct therapy. Previously, MIP has shown TLR2/9 mediated activation of antigen presenting cells/Th1 cells and their enhanced infiltration in mouse melanoma but the underlying mechanism by which it is modulating these immune cells is not yet known.ResultsThis study reports for the first time that MIP immunotherapy involves type 1 interferon (IFN) signaling as one of the major signaling pathways to mediate the antitumor responses. Further, it was observed that MIP therapy significantly influenced frequency and activation of different subsets of T cells like regulatory T cells (Tregs) and CD8+ T cells in the TME. It reduces the migration of Tregs into the TME by suppressing the expression of CCL22, a Treg recruiting chemokine on DCs and this process is dependent on type 1 IFN. Simultaneously, in a type 1 IFN dependent pathway, it enhances the activation and effector function of the immunosuppressive tumor resident DCs which in turn effectively induce the proliferation and effector function of the CD8+ T cells.ConclusionThis study also provides evidence that MIP induced pro-inflammatory responses including induction of effector function of conventional dendritic cells and CD8+ T cells along with reduction of intratumoral Treg frequency are essentially mediated in a type 1 IFN-dependent pathway. |
| first_indexed | 2024-04-09T18:07:30Z |
| format | Article |
| id | doaj.art-092f74b66ed84bf999cff1381b0f6e13 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T18:07:30Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-092f74b66ed84bf999cff1381b0f6e132023-04-14T05:13:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11047111104711Type 1 interferon mediated signaling is indispensable for eliciting anti-tumor responses by Mycobacterium indicus praniiGargi Roy0Anush Chakraborty1Bharati Swami2Lalit Pal3Charvi Ahuja4Soumen Basak5Sangeeta Bhaskar6Product Development Cell, National Institute of Immunology, New Delhi, IndiaProduct Development Cell, National Institute of Immunology, New Delhi, IndiaProduct Development Cell, National Institute of Immunology, New Delhi, IndiaProduct Development Cell, National Institute of Immunology, New Delhi, IndiaProduct Development Cell, National Institute of Immunology, New Delhi, IndiaSystems Immunology Lab, National Institute of Immunology, New Delhi, IndiaProduct Development Cell, National Institute of Immunology, New Delhi, IndiaIntroductionThe evolving tumor secretes various immunosuppressive factors that reprogram the tumor microenvironment (TME) to become immunologically cold. Consequently, various immunosuppressive cells like Tregs are recruited into the TME which in turn subverts the anti-tumor response of dendritic cells and T cells.Tumor immunotherapy is a popular means to rejuvenate the immunologically cold TME into hot. Mycobacterium indicus pranii (MIP) has shown strong immunomodulatory activity in different animal and human tumor models and has been approved for treatment of lung cancer (NSCLC) patients as an adjunct therapy. Previously, MIP has shown TLR2/9 mediated activation of antigen presenting cells/Th1 cells and their enhanced infiltration in mouse melanoma but the underlying mechanism by which it is modulating these immune cells is not yet known.ResultsThis study reports for the first time that MIP immunotherapy involves type 1 interferon (IFN) signaling as one of the major signaling pathways to mediate the antitumor responses. Further, it was observed that MIP therapy significantly influenced frequency and activation of different subsets of T cells like regulatory T cells (Tregs) and CD8+ T cells in the TME. It reduces the migration of Tregs into the TME by suppressing the expression of CCL22, a Treg recruiting chemokine on DCs and this process is dependent on type 1 IFN. Simultaneously, in a type 1 IFN dependent pathway, it enhances the activation and effector function of the immunosuppressive tumor resident DCs which in turn effectively induce the proliferation and effector function of the CD8+ T cells.ConclusionThis study also provides evidence that MIP induced pro-inflammatory responses including induction of effector function of conventional dendritic cells and CD8+ T cells along with reduction of intratumoral Treg frequency are essentially mediated in a type 1 IFN-dependent pathway.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1104711/fullMycobacterium indicus praniitumor immunotherapytype 1 interferon signalingdendritic cellsregulatory T cellsCD8+ T cells |
| spellingShingle | Gargi Roy Anush Chakraborty Bharati Swami Lalit Pal Charvi Ahuja Soumen Basak Sangeeta Bhaskar Type 1 interferon mediated signaling is indispensable for eliciting anti-tumor responses by Mycobacterium indicus pranii Frontiers in Immunology Mycobacterium indicus pranii tumor immunotherapy type 1 interferon signaling dendritic cells regulatory T cells CD8+ T cells |
| title | Type 1 interferon mediated signaling is indispensable for eliciting anti-tumor responses by Mycobacterium indicus pranii |
| title_full | Type 1 interferon mediated signaling is indispensable for eliciting anti-tumor responses by Mycobacterium indicus pranii |
| title_fullStr | Type 1 interferon mediated signaling is indispensable for eliciting anti-tumor responses by Mycobacterium indicus pranii |
| title_full_unstemmed | Type 1 interferon mediated signaling is indispensable for eliciting anti-tumor responses by Mycobacterium indicus pranii |
| title_short | Type 1 interferon mediated signaling is indispensable for eliciting anti-tumor responses by Mycobacterium indicus pranii |
| title_sort | type 1 interferon mediated signaling is indispensable for eliciting anti tumor responses by mycobacterium indicus pranii |
| topic | Mycobacterium indicus pranii tumor immunotherapy type 1 interferon signaling dendritic cells regulatory T cells CD8+ T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1104711/full |
| work_keys_str_mv | AT gargiroy type1interferonmediatedsignalingisindispensableforelicitingantitumorresponsesbymycobacteriumindicuspranii AT anushchakraborty type1interferonmediatedsignalingisindispensableforelicitingantitumorresponsesbymycobacteriumindicuspranii AT bharatiswami type1interferonmediatedsignalingisindispensableforelicitingantitumorresponsesbymycobacteriumindicuspranii AT lalitpal type1interferonmediatedsignalingisindispensableforelicitingantitumorresponsesbymycobacteriumindicuspranii AT charviahuja type1interferonmediatedsignalingisindispensableforelicitingantitumorresponsesbymycobacteriumindicuspranii AT soumenbasak type1interferonmediatedsignalingisindispensableforelicitingantitumorresponsesbymycobacteriumindicuspranii AT sangeetabhaskar type1interferonmediatedsignalingisindispensableforelicitingantitumorresponsesbymycobacteriumindicuspranii |