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B- and T-lymphocyte attenuator precursor (B- and T-lymphocyte-associated protein) (CD272 antigen)


Combinatorial approach to cancer immunotherapy: strength in numbers.

Immune-checkpoint blockade therapy with antibodies targeting CTLA-4 and PD-1 has revolutionized melanoma treatment by eliciting responses that can be remarkably durable and is now advancing to other malignancies. However, not all patients respond to immune-checkpoint inhibitors. Extensive preclinical evidence suggests that combining immune-checkpoint inhibitors with other anti-cancer treatments can greatly improve the therapeutic benefit. The first clinical success of the combinatorial approach to cancer immunotherapy was demonstrated using a dual-checkpoint blockade with CTLA-4 and PD-1 inhibitors, which resulted in accelerated FDA approval of this therapeutic regimen. In this review, we discuss the combinations of current and emerging immunotherapeutic agents in clinical and preclinical development and summarize the insights into potential mechanisms of synergistic anti-tumor activity gained from animal studies. These promising combinatorial partners for the immune-checkpoint blockade include therapeutics targeting additional inhibitory receptors of T cells, such as TIM-3, LAG-3, TIGIT, and BTLA, and agonists of T cell costimulatory receptors 4-1BB, OX40, and GITR, as well as agents that promote cancer cell recognition by the immune system, such as tumor vaccines, IDO inhibitors, and agonists of the CD40 receptor of APCs. We also review the therapeutic potential of regimens combining the immune-checkpoint blockade with therapeutic interventions that have been shown to enhance immunogenicity of cancer cells, including oncolytic viruses, RT, epigenetic therapy, and senescence-inducing therapy.

MeSH Terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols
  • Humans
  • Immunologic Factors
  • Immunotherapy
  • Neoplasms


  • immune checkpoints
  • immunogenic cell death
  • melanoma
  • senescence

BTLA expression declines on B cells of the aged and is associated with low responsiveness to the trivalent influenza vaccine.

Virus-neutralizing antibody and B cell responses to influenza A viruses were measured in 35 aged and 28 middle-aged individuals following vaccination with the 2012 and 2013 trivalent inactivated influenza vaccines. Antibody responses to the vaccine strains were lower in the aged. An analysis of B cell subsets by flow cytometry with stains for immunoregulators showed that B cells of multiple subsets from the aged as compared to younger human subjects showed differences in the expression of the co-inhibitor B and T lymphocyte attenuator (BTLA). Expression of BTLA inversely correlated with age and appears to be linked to shifting the nature of the response from IgM to IgG. High BTLA expression on mature B cells was linked to higher IgG responses to the H1N1 virus. Finally, high BTLA expression on isotype switched memory B cells was linked to better preservation of virus neutralizing antibody titers and improved recall responses to vaccination given the following year.

MeSH Terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • B-Lymphocytes
  • Biomarkers
  • Down-Regulation
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin G
  • Immunologic Memory
  • Immunophenotyping
  • Influenza A Virus, H1N1 Subtype
  • Influenza Vaccines
  • Male
  • Receptors, Immunologic
  • Time Factors
  • Vaccination


  • BTLA
  • Gerotarget
  • HSV
  • aging
  • immunosenescence
  • influenza