Spatial Heterogeneity of Intratumoral Microbiota: A New Frontier in Cancer Immunotherapy Resistance

The intratumoral microbiota, as an important component of the tumor microenvironment, is increasingly recognized as a key factor in regulating responses to cancer immunotherapy. Recent studies have revealed that the intratumoral microbiota is not uniformly distributed but instead exhibits significan...

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Main Authors: Qiwen Tan, Xiongjing Cao, Falong Zou, Hanwenchen Wang, Lijuan Xiong, Shenghe Deng
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/5/1261
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author Qiwen Tan
Xiongjing Cao
Falong Zou
Hanwenchen Wang
Lijuan Xiong
Shenghe Deng
author_facet Qiwen Tan
Xiongjing Cao
Falong Zou
Hanwenchen Wang
Lijuan Xiong
Shenghe Deng
author_sort Qiwen Tan
collection DOAJ
description The intratumoral microbiota, as an important component of the tumor microenvironment, is increasingly recognized as a key factor in regulating responses to cancer immunotherapy. Recent studies have revealed that the intratumoral microbiota is not uniformly distributed but instead exhibits significant spatial heterogeneity, with its distribution patterns influenced by factors such as tumor anatomy, local immune status, and therapeutic interventions. This spatial heterogeneity not only alters the interactions between microbes and the host immune system but may also reshape the immunogenic and immunosuppressive landscapes of tumors. The enrichment or depletion of microbiota in different tumor regions can influence immune cell infiltration patterns, metabolic pathway activities, and immune checkpoint molecule expression, thereby driving the development of resistance to immunotherapy. Moreover, certain bacterial metabolites form concentration gradients between the tumor core and margins, thereby regulating immune cell function. Therefore, understanding and manipulating the spatial distribution of intratumoral microbiota, particularly in resistant patients, holds promise for developing new strategies to overcome immunotherapy resistance. In the future, precise modulation strategies targeting microbial spatial heterogeneity, such as engineered bacterial vectors, probiotic combinations, and phage therapy, may open new avenues for immunotherapy.
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publishDate 2025-05-01
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spelling doaj-art-3746c0d12a5b4a2a906f7da240062ad42025-08-20T02:33:38ZengMDPI AGBiomedicines2227-90592025-05-01135126110.3390/biomedicines13051261Spatial Heterogeneity of Intratumoral Microbiota: A New Frontier in Cancer Immunotherapy ResistanceQiwen Tan0Xiongjing Cao1Falong Zou2Hanwenchen Wang3Lijuan Xiong4Shenghe Deng5Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Nosocomial Infection Management, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaThe intratumoral microbiota, as an important component of the tumor microenvironment, is increasingly recognized as a key factor in regulating responses to cancer immunotherapy. Recent studies have revealed that the intratumoral microbiota is not uniformly distributed but instead exhibits significant spatial heterogeneity, with its distribution patterns influenced by factors such as tumor anatomy, local immune status, and therapeutic interventions. This spatial heterogeneity not only alters the interactions between microbes and the host immune system but may also reshape the immunogenic and immunosuppressive landscapes of tumors. The enrichment or depletion of microbiota in different tumor regions can influence immune cell infiltration patterns, metabolic pathway activities, and immune checkpoint molecule expression, thereby driving the development of resistance to immunotherapy. Moreover, certain bacterial metabolites form concentration gradients between the tumor core and margins, thereby regulating immune cell function. Therefore, understanding and manipulating the spatial distribution of intratumoral microbiota, particularly in resistant patients, holds promise for developing new strategies to overcome immunotherapy resistance. In the future, precise modulation strategies targeting microbial spatial heterogeneity, such as engineered bacterial vectors, probiotic combinations, and phage therapy, may open new avenues for immunotherapy.https://www.mdpi.com/2227-9059/13/5/1261intratumoral microbiotaimmune microenvironmentspatial heterogeneityimmunotherapyresistance
spellingShingle Qiwen Tan
Xiongjing Cao
Falong Zou
Hanwenchen Wang
Lijuan Xiong
Shenghe Deng
Spatial Heterogeneity of Intratumoral Microbiota: A New Frontier in Cancer Immunotherapy Resistance
Biomedicines
intratumoral microbiota
immune microenvironment
spatial heterogeneity
immunotherapy
resistance
title Spatial Heterogeneity of Intratumoral Microbiota: A New Frontier in Cancer Immunotherapy Resistance
title_full Spatial Heterogeneity of Intratumoral Microbiota: A New Frontier in Cancer Immunotherapy Resistance
title_fullStr Spatial Heterogeneity of Intratumoral Microbiota: A New Frontier in Cancer Immunotherapy Resistance
title_full_unstemmed Spatial Heterogeneity of Intratumoral Microbiota: A New Frontier in Cancer Immunotherapy Resistance
title_short Spatial Heterogeneity of Intratumoral Microbiota: A New Frontier in Cancer Immunotherapy Resistance
title_sort spatial heterogeneity of intratumoral microbiota a new frontier in cancer immunotherapy resistance
topic intratumoral microbiota
immune microenvironment
spatial heterogeneity
immunotherapy
resistance
url https://www.mdpi.com/2227-9059/13/5/1261
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AT xiongjingcao spatialheterogeneityofintratumoralmicrobiotaanewfrontierincancerimmunotherapyresistance
AT falongzou spatialheterogeneityofintratumoralmicrobiotaanewfrontierincancerimmunotherapyresistance
AT hanwenchenwang spatialheterogeneityofintratumoralmicrobiotaanewfrontierincancerimmunotherapyresistance
AT lijuanxiong spatialheterogeneityofintratumoralmicrobiotaanewfrontierincancerimmunotherapyresistance
AT shenghedeng spatialheterogeneityofintratumoralmicrobiotaanewfrontierincancerimmunotherapyresistance