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Modeling combination chemo-immunotherapy for heterogeneous tumors

Shaoqing Chen1,2, Zheng Hu3, Da Zhou1,2

  • 1School of Mathematical Sciences Xiamen University Xiamen China.

Quantitative Biology (Beijing, China)
|February 12, 2026
PubMed

Insights

Chemotherapy can improve immunotherapy for hypermutable cancers by reducing tumor antigen diversity. Restoring the immune system post-chemotherapy is key for effective combination cancer treatment.

Area of Science:

  • Oncology
  • Immunotherapy
  • Mathematical Biology

Background:

  • Hypermutable cancers offer potential for immunotherapies like immune checkpoint blockade (ICB).
  • However, many hypermutated tumors exhibit poor prognosis due to diverse tumor antigen landscapes, with mechanisms poorly understood.
  • Understanding these mechanisms is crucial for developing effective cancer treatments.

Purpose of the Study:

  • To investigate the mechanisms governing treatment responses in heterogeneous tumors.
  • To explore the impact of combining chemotherapy and ICB therapy on hypermutable, antigenically diverse tumors using mathematical modeling.

Main Methods:

  • Development of mathematical models to simulate tumor-immune dynamics.
  • Analysis of the effects of chemotherapy on tumor antigenic heterogeneity.
  • Evaluation of the combined impact of chemotherapy and ICB therapy.

Main Results:

  • Chemotherapy was found to reduce antigenic heterogeneity within tumors.
  • This reduction in heterogeneity creates more favorable immunological conditions for ICB therapy.
  • The recovery of the immune system following chemotherapy is essential for enhancing the efficacy of combined chemo-ICB therapy.

Conclusions:

  • Combining chemotherapy with ICB therapy can overcome poor prognosis in hypermutable cancers by reducing antigenic heterogeneity.
  • Mathematical modeling provides insights into optimizing combination cancer immunotherapies.
  • Immune system recovery post-chemotherapy is a critical factor for successful chemo-ICB treatment strategies.
Keywords:
chemo‐immunotherapyimmune checkpoint blockademathematical modelingneoantigen heterogeneitytreatment strategy

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