Stop and go: hematopoietic cell transplantation in the era of chimeric antigen receptor T cells and checkpoint inhibitors

Abstract

Purpose of review For several decades, hematopoietic cell transplantation has been considered the standard curative therapy for many patients with hematological malignancies. In addition to the cytotoxic effects of the chemotherapy and radiation used in the conditioning regimen, the benefits of hematopoietic cell transplantation are derived from a reset of the immune system and harnessing the ability of donor T cells to eliminate malignant cells. With the dawn of the era of immunotherapies in the form of checkpoint inhibitors and chimeric antigen receptor T cells, the role of hematopoietic cell transplantation has evolved. Recent findings Immunotherapy with checkpoint inhibitors is increasingly being used for relapsed Hodgkin and non-Hodgkin lymphoma after autoHCT. Checkpoint inhibitors are also being tested after alloHCT with observable benefits in treating hematological malignancies, but with a potential risk of increased GVHD and transplant-related mortality. Immunotherapy with CD19 CAR T cells are powerful options with aggressive B cell malignancies both for therapy and as induction leading to alloHCT. Summary While immunotherapies with checkpoint inhibition and CAR T cells are increasing being used to treat hematological malignancies, HCT remains a standard of care for most of the diseases with the best chance of cure. Combination of these therapies with HCT has the potential to more effectively treat hematological malignancies.

Chemotherapy reinforces anti-tumor immune response and enhances clinical efficacy of immune checkpoint inhibitors

“…Common action mechanisms of chemotherapeutic agents are 1. Marked lymphodepletion or so-called ‘reset’ of the immune system (with major adverse effects) and near-to-complete reconstitution of the host’s immunological repertoire ( 57 ), 2. Decrease immunosuppressive cells, including M2-like tumor-associated macrophages (TAMs), MDSCs, and Tregs, by providing an inflammatory condition ( 17 , 58 , 59 ), or 3.…”

Nano-Chemotherapy synergize with immune checkpoint inhibitor- A better option?

“…Traditional chemotherapy might suppress the immune system by causing lymphocyte depletion ( 33 , 34 ), which might be detrimental to cancer treatment basing on normal quantity and function of T cells, such as immune checkpoint inhibitor. Although the depletion of lymphocytes might restart the immune system so that the immune system can better fight against tumors ( 35 ), this theory has not been confirmed. In addition, doxorubicin and gemcitabine have been found to increase circulating MDSC cells in patients ( 36 ), which might worsen the tumor immune micro-environment.…”