Inclusion Criteria:

• Age ≥ 18 years old.
• Histological and/or Radiologic confirmation of HCC OR Histologic confirmation of intrahepatic CCA.
• The following tumor characteristics must be met:
  • Unresectable HCC or intrahepatic CCA;
  • Measurable or evaluable disease;
  • All lesions should be treatable by EBRT while meeting normal tissue constraints;
  • Tumor lesions should be accessible using an US guided approach for intratumoral DC injection;
  • Patients are required to have no evidence of extrahepatic tumor (excluding tumor thrombus) by computed tomography (CT) or magnetic resonance imaging (MRI) scan NOTE: Patients who are not candidates for surgical treatment or for ablation with curative intent are allowed.
• Good candidate for standard of care high-dose conformal EBRT in the view of the investigator.
• ECOG Performance Status (PS) 0 or 1.
• The following laboratory values obtained ≤14 days prior to registration:
  • Absolute neutrophil count (ANC) ≥1000/mm3;
  • Absolute lymphocyte count (ALC) ≥500/mm3;
  • Absolute monocyte count (AMC) ≥300/mm3;
  • Platelet count ≥50,000/mm3;
  • Hemoglobin ≥9.0 g/dL;
  • Total bilirubin <3 mg/dL;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 x ULN;
  • Creatinine ≤2 mg/dL;
  • PT/INR ≤1.5 x ULN.
• Negative pregnancy test done ≤7 days prior to registration, for persons of childbearing potential only.
• Ability to provide written consent.
• Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Willingness to provide blood and tissue samples for correlative research purposes.

Exclusion Criteria

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant persons;
  • Nursing persons;
  • Persons of childbearing potential who are unwilling to employ adequate contraception .
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy.
  • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving any other investigational agent that would be considered a treatment for the primary neoplasm.
• Other active malignancy ≤3years prior to registration.
  • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
  • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer.
• Major surgery ≤4 weeks prior to enrollment (other than diagnostic surgery or surgical spacer placement in preparation for radiation treatment).
• History of hypersensitivity or anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid.
• Active autoimmune disease such as autoimmune hepatitis, Crohn’s disease, rheumatoid arthritis, Sjögrens’ disease, systemic lupus erythematosus, or similar conditions.
• Requires coagulopathy treatment (INR >1.5) or use of anti-platelet agents that cannot be discontinued for the intratumoral injection procedure.
  • NOTE: Heparin for line patency without detectable lab abnormalities in coagulation will be allowed.
• Corticosteroids ≤2 weeks prior to registration, including oral, IV, subcutaneous, or inhaled routes of administration.
  • NOTE: Patients on chronic corticosteroids for adrenal insufficiency or other reasons may enroll if they receive less than 10 mg/day of prednisone (or equivalent).
• History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• Child Pugh class B or C cirrhosis of the liver.
• Previously received immune modulating therapies including but not limited to immune checkpoint inhibitors targeting PD-1 PDL-1 CTLA4, etc; or prior dendritic cell therapy.
• Prior liver radiation, including radioembolization.
• BCLC stage D disease (Llovet, Di Bisceglie et al. 2008.