Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients

  title={Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients},
  author={Erez Nissim Baruch and Ilan Youngster and Guy Ben-betzalel and Rona Ortenberg and Adi Lahat and Lior H Katz and K M Adler and Daniela Dick-Necula and Stephen P. Raskin and Naamah Bloch and Daniil Rotin and Liat Anafi and Camila Avivi and Jenny Melnichenko and Yael Steinberg-Silman and Ronac Mamtani and Hagit Harati and Nethanel Asher and Ronnie Shapira-Frommer and Tal Brosh-Nissimov and Yael Eshet and Shira Ben-Simon and Oren Ziv and Md Abdul Wadud Khan and Moran Amit and Nadim J. Ajami and Iris Barshack and Jacob Schachter and Jennifer A. Wargo and Omry Koren and Gal Markel and Ben Boursi},
  pages={602 - 609}
New fecal microbiota for cancer patients The composition of the gut microbiome influences the response of cancer patients to immunotherapies. Baruch et al. and Davar et al. report first-in-human clinical trials to test whether fecal microbiota transplantation (FMT) can affect how metastatic melanoma patients respond to anti–PD-1 immunotherapy (see the Perspective by Woelk and Snyder). Both studies observed evidence of clinical benefit in a subset of treated patients. This included increased… 

Fecal microbiota transplantation: can it circumvent resistance to PD-1 blockade in melanoma?

Two experiments supported the rationale to treat cancer patients who failed a firstor second-line immunotherapy with FMT derived from an R patient with the first proof-of-concept that fecal microbiota transplantation (FMT) transfer clinical benefit in metastatic melanoma patients primarily resistant to immune checkpoint blockade (ICB).

Using the canine microbiome to bridge translation of cancer immunotherapy from pre-clinical murine models to human clinical trials

Together, pre-clinical mechanistic studies and large animal trials can help fully unlock the potential of the microbiome as a diagnostic and therapeutic target in cancer.

Gut Microbiota and Antitumor Immunity: Potential Mechanisms for Clinical Effect

How gut microbiota may affect the activity of immune cells by at least three interlacing mechanisms: activation of pattern recognition receptors, molecular mimicry, and impact of metabolites is discussed.

Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy.

It is concluded that changes in the intestinal microbiome are associated with clinical outcomes after anti-CD19 CAR T cell therapy in patients with B cell malignancies.

Antitumor effects of fecal microbiota transplantation: Implications for microbiome modulation in cancer treatment

This review systematically summarizes the role of microbes and their metabolites in the regulation of tumor immunity and highlights the mechanism of action of FMT in the treatment of refractory tumors as well as in improving the efficacy of immunotherapy.

The role of gut microbiome in immune modulation in metastatic renal cell carcinoma

The role of the microbiome and its bidirectional interaction with ICIs and other drugs will be explored, with a particular focus on the microbiome profile in RCC.

Commensal Microbiota and Cancer Immunotherapy: Harnessing Commensal Bacteria for Cancer Therapy

The immunological roles of commensal microbiota in cancer treatment are summarized and specific examples of bacteria that show anticancer effect when administered as a monotherapy or as an adjuvant agent for immunotherapy are given.

Local tumor microbial signatures and response to checkpoint blockade in non-small cell lung cancer

Correlations with clinical data revealed that high microbial diversity was associated with improved patient survival irrespective of radiology-based treatment response, and the presence of Gammaproteobacteria correlated with low PD-L1 expression and poor response to checkpoint-based immunotherapy, translating into poor survival.

Fecal microbiota transplantation for immunotherapy‐resistant urological tumors: Is it time? An update of the recent literature

The aim of this commentary is to highlight the potential for FMT in urological tumors (UC, RCC, and PCa) resistant to ICIs and to provide the evidence behind this distinct breakthrough.

Blood microbiota diversity determines response of advanced colorectal cancer to chemotherapy combined with adoptive T cell immunotherapy

The diversity of the blood microbiome is a promising predictive marker for clinical responses to chemotherapy combined with DC-CIK, and more diverse blood microbiota that included Bifidobacterium, Lactobacillus, and Enterococcus were identified amongresponders compared with non-responders.



Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients

Examination of the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients.

Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

It is found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition, and Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer.

The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients

The results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients and could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti–PD-L1 therapy.

Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota

A key role is revealed for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade, which is found to depend on distinct Bacteroides species in mice and patients.

Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy

Comparison of melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, suggests that manipulating the microbiota may modulate cancer immunotherapy.

Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12.

It is reported that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer.

Abstract IA28: Targeting the microbiome in cancer immunotherapy

Some recent analysis of the role of the microbiome in anti-PD1 therapy in melanoma patients, the preliminary data of a fecal microbiota transfer clinical trial (performed at the University of Pittsburgh Cancer Center), as well as mouse data on the effect of dietary fibers on anti- PD1 cancer therapy are discussed.

T Cell–Inflamed versus Non-T Cell–Inflamed Tumors: A Conceptual Framework for Cancer Immunotherapy Drug Development and Combination Therapy Selection

To maximize the impact of immunotherapy drug development, pretreatment stratification of targets associated with either the T cell–inflated or noninflamed tumor microenvironment should be employed and biomarkers predictive of responsiveness to specific immunomodulatory therapies should guide therapy selection.

Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis.

FMT increased microbial diversity and altered composition, based on analyses of colon and fecal samples collected before vs after FMT, and associated specific bacteria and metabolic pathways with induction of remission.