Does chemotherapy augment anti-tumor immunotherapy by preferential impairment of regulatory T cells?
Chemotherapy, the treatment modality of choice for advanced cancers, is considered immunosuppressive due to its depletion of immune cells. Hence, chemotherapy is traditionally thought to adversely affect anti-tumor immune responses and antagonistic to tumor immunotherapy. Contrary to conventional belief, recent studies have shown that combining chemotherapy with immunotherapy resulted in enhanced anti-tumor immunity and improved therapeutic outcome. The mechanisms by which the use of chemotherapy paradoxically benefits immunotherapy await elucidation. CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) are a lymphocyte subset which plays a crucial role in inhibiting tumor-reactive effector cell functions and suppressing anti-tumor immunity. We hypothesize that chemotherapy benefits immunotherapy by preferentially impairing Treg, in effect eliminating immunosuppressive elements and augmenting the immune function of anti-tumor effector cells. Clarification of how chemotherapy exerts its immunomodulatory effects will aid in the development of better combination strategies of chemoimmunotherapy in the treatment of cancer.
Zhang
Lei
L
Department of Immunology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, PR China.
Dermawan
Kam-tai
KT
Jin
Mei-lin
ML
Xiong
Si-dong
SD
Chu
Yi-wei
YW
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003131:Combined Modality Therapy / Q000379:methods; D004358:Drug Therapy / Q000379:methods; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008495:Medical Oncology / Q000379:methods; D008954:Models, Biological; D008962:Models, Theoretical; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D000970:Antineoplastic Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit